Medical Dosimetry

SBRT of superior liver lesions using Acuros XB calculation algorithm and 10 MV FFF
beams: a search of acceptable MLC margins
--Manuscript Draft--

Manuscript Number:

Article Type: Research Article

Section/Category: Dosimetry Contribution

Keywords: Liver SBRT; 10 MV FFF beams; AcurosXB; MLC margins; heterogeneity

Corresponding Author: Nathan Jones, B.S.

University of Rochester Medical Center
Rochester, ny UNITED STATES

First Author: Neil Joyce, B.S., CMD, R.T.(T)

Order of Authors: 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, Ph.D., CMD, R.T.(R)(T), FAAMD

Ashley Hunzeker, M.S., CMD

Matt Tobler, M.S., CMD, R.T.(T)

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Cover Letter

Nathan Jones B.S., CMD, R.T.(R)

University of Wisconsin – La Crosse
Medical Dosimetry Program

Editor – in – Chief
Medical Dosimetry

December 2, 2019

Dear Editor,
Please consider this submission of an original research paper for publication in the Medical
Dosimetry Journal. We believe this manuscript is appropriate for publication because it addresses
a gap in literature that has not been discussed. This manuscript has not been published and it is
not under consideration for publication elsewhere. We have no conflicts of interest to disclose.

Sincerely,
Nathan Jones, B.S., CMD, R.T.(R)

Title of Manuscript: SBRT of superior liver lesions using Acuros XB calculation algorithm and
10 MV FFF beams: a search of acceptable MLC margins
Authors:
First
Authorship Last Name Credentials Email
Name
 1st author Neil Joyce B.S., CMD, R.T.(T) Neil_Joyce@urmc.rochester.edu
 2nd author Amy Herman B.S., CMD, R.T.(T) Amy_Herman@urmc.rochester.edu
 3rd author* Nathan Jones B.S., CMD, R.T.(R) Nathan_Jones@urmc.rochester.edu
PhD, CMD,
 4th author Nishele Lenards nlenards@uwlax.edu
R.T.(R)(T), FAAMD
 5th author Ashley Hunzeker M.S., CMD ahunzeker@uwlax.edu
 6th author Matt Tobler CMD, R.T.(T) mtobler@uwlax.edu
* denotes corresponding author
 denotes student/graduate
 denotes instructors/program officials
 denotes advisors/adjunct faculty

Affiliation: Medical Dosimetry Program at the University of Wisconsin, La Crosse, WI

1725 State St, La Crosse, WI 54601
Manuscript Click here to view linked References

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4 SBRT of superior liver lesions using Acuros XB calculation algorithm and 10 MV FFF
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6 beams: a search of acceptable MLC margins
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8 Neil Joyce, B.S., CMD, R.T.(T); Amy Herman, B.S., CMD, R.T.(T); Nathan Jones, B.S., CMD,
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10 R.T.(R); Nishele Lenards, PhD, CMD, R.T.(R)(T), FAAMD; Ashley Hunzeker, M.S., CMD;
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12 Matt Tobler, CMD, R.T.(T)
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14
Medical Dosimetry Program, University of Wisconsin-La Crosse, La Crosse, WI
15 ABSTRACT
16
17 Dosimetric coverage to planning target volume (PTV) at the dome of the liver which
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19 includes or abuts tissues of low densities such as lung parenchyma, can prove to be challenging.
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21 In comparison to Acuros XB algorithm (AXB), the Analytical Anisotropic Algorithm (AAA) has
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23 been found to be an inferior dose calculation engine, especially in areas with a high degree of
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25
heterogeneity. Previous studies identified optimal 10 MV flattening filter-free (FFF) multi-leaf
26 collimator (MLC) margins in the SBRT treatment of liver lesions. To date, no studies were
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28 specific to PTVs at the dome of the liver which are associated with tissues of low densities. The
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30 use of an advanced calculation model such as the AXB algorithm may have an impact on the
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32 suitable MLC margins for these regions.
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34 The aim of the current study was to determine acceptable 10 MV FFF beam MLC
35
margins in the stereotactic body radiation therapy (SBRT) of dome of the liver lesions using the
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37 AXB algorithm. This research focused on 10 patients who were treated for primary liver cancer
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39 or liver metastases located at the dome. Optimized AXB plans were analyzed to determine
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41 acceptable MLC margins considering several plan metrics. The results support previous studies
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43 which identified the MLC margins of -1.0 mm and 0.0 mm providing acceptable normal liver
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45 tissue sparing in addition to having favorable conformity index (CI) values.
46 Keywords: Liver SBRT, 10 MV FFF beams, AcurosXB, MLC margins, heterogeneity
47
48 Introduction
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50 Stereotactic body radiation therapy (SBRT) for the treatment of liver cancer or liver
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52 metastases has been shown to be safe and provide excellent outcomes.1,2 Treatment planning
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54 goals in SBRT are to deliver the prescribed therapeutic radiation dose to the planning target
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56 volume (PTV) and ensure rapid dose fall-off from the PTV to provide needed organs at risk
57 (OAR) sparing. Dosimetric coverage of PTV is essential to achieve goals of both local control
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59 (LC) and overall survival (OS). Researchers have previously shown superior outcomes in both
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4 LC and OS in patients treated with liver SBRT when a biologically effective dose of 100 Gy
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6 (BED100Gy) or more is delivered.3,4 Inherent risks of increased doses to OAR are associated with
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8 SBRT and special considerations must be made during treatment planning.5 Challenges in
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10 gaining adequate dosimetric coverage to the PTV can arise when the PTV is surrounded by,
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12 includes, or abuts tissues of low density such as lung parenchyma.
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14
Differing dose calculation algorithms can result in dissimilar calculated doses of both
15 OAR and PTV that neighbor or include tissues of low densities. Clinical implications such as
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17 overestimation of tissues at the lung interface with the Analytical Anisotropic Algorithm (AAA)
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19 could become a concern.6 The AAA algorithm has the tendency to overestimate the median and
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21 mean dose to the PTV and gross tumor volume (GTV) respectively, which in turn has the
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23 potential to directly affect clinical outcomes.7 Although the AAA algorithm is more widely used
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in clinical routine, the Acuros XB algorithm (AXB) has been shown to more accurately model
26 dose distributions, especially in tissue with high heterogeneity such as lung parenchyma.7,8,9
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28 As treatment facilities replace older generation linear accelerators with modern versions,
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30 a greater number of patients will receive stereotactic radiation therapy treatments with state-of-
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32 the-art equipment with enhanced features such as flattening filter-free (FFF) beams. The
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34 utilization of FFF beams, when available to clinicians, has become the standard for both
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stereotactic radiosurgery (SRS) and SBRT. The dramatic increased dose rate of FFF beams in
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37 comparison to flattening filter (FF) beams enables a decrease in treatment delivery times with
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39 reduction in OAR and PTV intra-fraction motion. Through the advent of FFF beams in radiation
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41 therapy, benefits of both efficient treatment delivery and enhanced patient comfort were
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43 discovered.10 Flattening filter free beams have several advantages over FF beams including an
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45 increased dose rate factor of 2 to 4, decreased production of head scatter, and less lateral
46 transport due to a softer beam spectra.11 Flattening filter free beams and the effects of OAR
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48 sparing and PTV coverage have been studied. Yan et al12 found that although PTV coverage was
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50 similar between 10 MV FFF and FF beams, differences in OAR sparing with FFF beam was
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52 significant for some treatment sites, such as head and neck.
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54 When treating with SBRT, appropriate multi-leaf collimator (MLC) margins need to be
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56 established for the intended therapy to be both safe and efficacious. The large radiation doses
57 intrinsic to SBRT not only have an ablative effect on the tumor, but also carry potential risk of
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59 damage to OAR. In the SBRT treatment of liver lesions, an optimal 10 MV FFF beam MLC
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4 margin surrounding PTV was investigated. Ogata et al13 identified suitable MLC margins in
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6 patients treated with liver SBRT and 10 MV FFF beams, but the study was limited in that the
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8 liver PTV did not include the dome of the liver and the AXB algorithm was not used.
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10 To date, there has been a paucity of literature regarding appropriate MLC margins with
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12 the AXB algorithm in treatment planning for areas with high degree of tissue inhomogeneity.
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More specifically, the suitable 10 MV FFF beam MLC margins using the AXB algorithm with
15 SBRT to dome of liver lesions are not known. The problem is the optimal MLC margin may
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17 impact PTV coverage and OAR sparing with clinical implications.6,7 The purpose of the study
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19 was to determine acceptable 10 MV FFF beam MLC margins in SBRT of dome of the liver
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21 lesions using the AXB algorithm and the potential clinical effect.
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23 Based on the known differences between algorithms, the question arises if the MLC
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margins that were determined using AAA are still appropriate when using AXB. The null
26 hypotheses for the current study was that the AXB algorithm had no effect on the optimal 10 MV
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28 FFF MLC margins in areas of high tissue heterogeneity relative to PTV coverage (H10 - H20),
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30 plan quality indices (H30 - H50), and liver OAR sparing (H60 - H70) respectively. Using Dunn’s
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32 multiple comparison procedure, metrics were evaluated across multiple MLC margins and tested
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34 for significant differences in the distribution of responses for the variables. A family-wise error
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rate of 5% was used for each parameter.
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37 Methods and Materials
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39 Patient Selection & Setup
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41 For this single institution retrospective study, 10 patients who were treated for primary
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43 liver cancer or liver metastases located at the dome of the liver were selected for the study. The
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45 PTV selection criteria was limited to those with inclusion of the lung after GTV expansion. The
46 range of lung as part of the PTV studied was 2.1% to 22.5%, with mean value of 10.6%. This
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48 study excluded patients with PTV having < 2.0% of lung parenchyma included.
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50 Computed tomography (CT) scans were obtained with the patient in supine orientation
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52 with head towards the gantry and both arms above head. Treatment planning CT scans were
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54 acquired on a General Electric LightSpeed 16 slice scanner with 2.5 mm slice thickness during
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56 end expiratory breath-hold phase for simulation and subsequent treatment. Varian Real-Time
57 Position Management (RPM) system was utilized during simulation to track the patient breathing
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59 cycle and allow gated treatment planning CT acquisition. Immobilization devices used included
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 1 4
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4 a headrest, Vac-Lok bag under the head through the hips, Civco wingboard, and a triangle
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6 sponge under the knees with feet banded (Figure 1).
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8 Contouring
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10 The GTV was delineated on the treatment planning CT scan by the attending physician in
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12 Varian Eclipse version 13.6 treatment planning system (TPS). Due to patient simulation and
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treatment in end expiratory breath-hold phase, an Internal Target Volume (ITV) was not utilized.
15 The PTV was then generated by a GTV expansion of 1.0 cm in the superior and inferior
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17 directions and 0.5 cm radially. Planning target volumes ranged between 7.8 cm3 and 59.4 cm3 in
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19 the selected patient cohort. Organs at risk volumes including the liver, spinal cord, heart, lungs,
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21 and esophagus were outlined by the planning medical dosimetrist. The liver volume was
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23 specified as normal liver minus GTV.
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25
Treatment Planning
26 All 10 patients selected for this study were planned for 50 Gy to be delivered to the PTV
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28 at 10 Gy per fraction for 5 fractions. Treatment plans were created in Eclipse version 13.6
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30 utilizing a dynamic conformal arc (DCA) technique consisting of 6 non-coplanar arcs, with
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32 between 35° and 60° travel range for each. A calculation grid size of 0.25 cm was used for all
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34 plans. The goals were to create a conformal dose distribution surrounding PTV and to meet OAR
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dose constraints such as normal liver dose levels, recommended by Pollom et al14, for patients
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37 receiving abdominal SBRT. For the scope of this research, OAR analysis was limited to the liver.
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39 Flattening filter free 10 MV photon beams with dose rate of 2400 monitor units (MUs) per
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41 minute were used in planning for treatment on a Varian TrueBeam linear accelerator with 120
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43 MLC system. Optimized DCA treatment plans using the AXB algorithm were generated to
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45 evaluate PTV coverage, normal liver sparing, and plan quality metrics. The uniform MLC
46 margins ranged between -3.0 mm to 5.0 mm in 1.0 mm increments. Plans were normalized such
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48 that 95% of the PTV was encompassed by the prescription dose of 50 Gy (D95% = 50 Gy).
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50 Plan Comparisons
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52 To quantify differences between the AAA and AXB algorithms in the study sample, plan
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54 result comparisons were made between optimized AAA and AXB treatment plans recalculated
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56 with AAA MU (Table 1). Wilcoxon signed rank tests were used rather than paired t-tests due to
57 small sample sizes and non-normality observed in some of the data samples. The Benjamini-
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59 Hochberg adjustment was made for each parameter with a family-wise error rate of 5% to
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 1 5
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4 control Type 1 error rate for multiple testing over the 9 MLC margins studied. P-values of < 0.05
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6 were considered to be statistically significant. The quality indices and metrics used in analysis
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8 included dose received by 99% of PTV volume (D99%), D95%, and mean PTV dose (PTV Dmean).
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10 The AAA algorithm was confirmed to overestimate PTV doses as observed in previous
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12 studies.7,8,9
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Optimized AXB plan metrics used in analysis included PTV D99%, PTV Dmean,
15 homogeneity index (HI) defined as dose received by 5% of volume (D5%) divided by D95%,
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17 Radiation Therapy Oncology Group (RTOG) conformity index (CIRTOG) defined as prescription
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19 isodose volume (PIV) divided by target volume (TV), gradient index (GI) defined as half
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21 prescription isodose volume (PIVhalf) divided by PIV, mean liver dose (liver Dmean), and volume
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23 of liver receiving 20 Gy or more (liver V20Gy). Conformity index is an important tool to assess
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25
the degree of how well a planned dose distribution conforms to the PTV with favorable CI values
26 limiting dose to surrounding normal tissues. As defined by the RTOG, normal CIRTOG value
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28 range is 1.0 – 2.0, with major deviation greater than 2.5. Optimal HI values are observed when at
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30 or near 1.0, an indication of ideal dose homogeneity. The GI is used as a tool to compare
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32 treatment plans with similar conformity, but with variance in dose gradients. Plans with lower GI
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34 values indicate a steeper dose gradient as compared to plans with higher GI values and
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subsequently indicate greater normal tissue sparing.
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37 Statistical Analysis
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39 For each of the dosimetric parameters evaluated with optimized AXB plans, Dunn’s
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41 multiple comparison procedure was used to compare the distributions of responses among the
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43 MLC margins with a family-wise error rate of 5% used for each parameter. The P-values of >
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45 0.05 were considered not significant from the optimal value in the population. Optimal MLC
46 margins were identified for each metric studied. In the population distribution, the MLC margins
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48 considered not significantly different can all be deemed optimal since the populations do not
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50 differ. The Benjamini-Hochberg adjustment was made for each parameter with a family-wise
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52 error rate of 5% to control Type 1 error rate for multiple testing over the 9 MLC margins studied.
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54 All statistical analyses were performed using R (R Core Team, 2019).
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56 Results
57 PTV
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 1 6
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4 The PTV D99% and PTV Dmean results displayed a quadratic trend with increasing MLC
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6 margins (Figures 2,3). The minimum mean (± SD) PTV D99% was found to be 38.34 (± 1.32)
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8 Gy with -3.0 mm MLC margins, with maximum mean of 48.24 (± 0.67) Gy observed with 5.0
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10 mm MLC margins. The optimal PTV D99% value in the sample (Table 2) occurred at MLC
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12 margin of 5.0 mm and the population distributions at MLC margins 2.0, 3.0, and 4.0 were not
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14 significantly different from 5.0 mm MLC margins (P = 0.0902, P = 0.2732, P = 0.6812,
15 respectively). The population distributions at MLC margins of -3.0 mm, -2.0 mm, -1.0 mm, 0.0
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17 mm, and 1.0 mm were significantly different from the distribution using 5.0 mm margins (P <
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19 0.0005, P < 0.0005, P < 0.0005, P < 0.0005, P = 0.0112 respectively). The H10 was not rejected
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21 due to the quadratic relationship between of PTV D99% metrics and MLC margins.
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23 The maximum mean PTV Dmean was 84.09 (± 5.75) Gy with -3.0 mm MLC margins and
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25 minimum mean PTV Dmean of 54.16 (± 0.70) Gy delivered with 5.0 mm margins (Table 2).The
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optimal PTV Dmean value in the study sample (Table 2) occurred at MLC margin of -3.0 mm and
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28 the population distributions at MLC margins -2.0 mm and -1.0 mm were not significantly
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30 different from -3.0 mm MLC margins (P = 0.4016 and P = 0.0886 respectively). The population
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32 distributions at MLC margins of 0.0 mm, 1.0 mm, 2.0 mm, 3.0 mm, 4.0 mm, and 5.0 mm were
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34 significantly different from the distribution using -3.0 mm margins (P = 0.0104, P = 0.0006, P <
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36 0.0005, P < 0.0005, P < 0.0005, and P < 0.0005 respectively). In comparison to the PTV D99%,
37 an inverse relationship was revealed with the PTV Dmean metric (Figure 3). The H20 was not
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39 rejected due to the quadratic relationship between of PTV Dmean metrics and MLC margins.
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41 Indices Evaluation
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43 The HI values were found to increase quadratically with decreasing MLC margins
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45 (Figure 4). The mean HI was the least with 5.0 mm MLC margins (Table 3) at 1.15 (± 0.03) with
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47 -3.0 MLC margins resulting in the highest mean HI value of 2.16 (± 0.25). The optimal HI value
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in the study sample occurred at MLC margin of 5.0 mm and the population distributions at MLC
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50 margins 2.0 mm, 3.0 mm, and 4.0 mm were not significantly different from -5.0 mm MLC
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52 margins (P = 0.0626, P = 0.3292, and P = 0.7482 respectively). The population distributions at
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54 MLC margins of -3.0 mm, -2.0 mm, -1.0 mm, 0.0 mm, and 1.0 mm were significantly different
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56 from the distribution using 5.0 mm margins (P < 0.0005, P < 0.0005, P < 0.0005, P = 0.002, and
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58 P = 0.0040 respectively). The H30 was not rejected due to the quadratic relationship between HI
59 metrics and MLC margins.
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4 The lowest mean CI was found to be 1.18 (± 0.10) with 0.0 mm MLC margins in
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6 optimized AXB plans (Figure 5). The optimal CI value in the study sample occurred at MLC
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8 margin of 0.0 mm (Table 3) and the population distributions at MLC margins -2.0 mm, -1.0 mm,
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10 1.0 mm and 2.0 mm were not significantly different from 0.0 mm MLC margins (P = 0.0514, P
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12 = 0.5954, P = 0.6968, and P = 0.1654 respectively). The population distributions at MLC
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14 margins of -3.0 mm, 3.0 mm, 4.0 mm, and 5.0 mm were found to be significantly different from
15 the distribution using 0.0 mm margins (P < 0.0005, P = 0.0168, P = 0.0008, and P < 0.0005
16
17 respectively). The CI analysis did not indicate rejection of H40 due to similarities in comparison
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19 to results of previous studies.13
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21 Gradient index values generally increased with MLC margin (Figure 6). The minimum
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23 mean GI of 2.99 (± 0.25) was found to be as a result of -2.0 mm margins and maximum of 3.83
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25 (± 0.54) with 5.0 mm margins (Table 3). The optimal GI value in the study sample occurred at
26 MLC margin of -2.0 mm and the population distributions at MLC margins -3.0 mm, -1.0 mm,
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28 0.0 mm and 1.0 mm were not significantly different from -2.0 mm MLC margins (P = 0.8238, P
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30 = 0.864, P = 0.4882, and P = 0.1192 respectively). The population distributions at MLC margins
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32 of 2.0 mm, 3.0 mm, 4.0 mm, and 5.0 mm were significantly different from the distribution using
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34 -2.0 mm margins (P = 0.0166, P = 0.0036, P < 0.0005, and P < 0.0005 respectively). The H50
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36 was not rejected due to the quadratic relationship between GI results and MLC margins.
37 Liver
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39 The mean liver Dmean across all MLC margins was found to be 5.90 Gy (Table 4). In the
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41 optimized AXB plans studied, the mean liver Dmean values were the least with 5.41(± 2.87) Gy
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43 using 0.0 mm margins and 5.47 (± 2.91) Gy with -1.0 mm MLC margins. The highest mean
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45 liver Dmean of 6.69 (± 3.35) Gy was observed with 5.0 mm margins (Figure 7). The optimal liver
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47 Dmean value in the study sample occurred at MLC margin of 0.0 mm and the population
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distributions at MLC margins -3.0 mm, -2.0 mm, -1.0 mm, 1.0 mm, 2.0 mm, 3.0 mm, 4.0 mm,
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50 and 5.0 mm were not significantly different from 0.0 mm MLC margins (P = 0.436, P = 0.7064,
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52 P = 0.9046, P = 0.8238, P = 0.6256, P = 0.4722, P = 0.325, and P = 0.2146 respectively). Upon
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54 analysis of liver Dmean metrics in correspondence with previous studies13, the H60 was not
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56 rejected.
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58 In terms of the mean liver V20Gy, a quadratic trend was observed between 0.0 mm and 5.0
59 mm MLC margins (Figure 8). The minimum mean liver V20Gy of 83.2 (± 43.75) cm3 and 83.3 (±
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4 44.14) cm3 was delivered with 0.0 mm and -1.0 mm MLC margins respectively (Table 4). The
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6 optimal mean liver V20Gy value in the study sample occurred at MLC margin of 0.0 mm and the
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8 population distributions at MLC margins -3.0 mm, -2.0 mm, -1.0 mm, 1.0 mm, 2.0 mm, 3.0 mm,
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10 and 4.0 mm were not significantly different from 0.0 mm MLC margins (P = 0.3552, P = 0.6812,
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12 P = 0.959, P = 0.758, P = 0.4616, P = 0.2376, and P = 0.0986 respectively). The population
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distribution at MLC margin of 5.0 mm was significantly different from the distribution using 0.0
15 mm margins (P = 0.0480). Similar to the analysis of liver Dmean, V20Gy metrics also correspond
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17 with previous studies13 resulting in the H70 not being rejected.
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19 Discussion
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21 In this study, the optimal 10 MV FFF beam MLC margins for PTV at the dome of the
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23 liver were investigated. The PTV D99%, PTV Dmean, and HI were found to follow a quadratic
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25
trend among MLC margins studied. Given the direct relationship between MLC margins and
26 PTV metrics, 5.0 mm MLC margins resulted in the highest mean PTV D99% and least mean PTV
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28 Dmean. The -3.0 mm MLC margins produced the lowest mean PTV D99% and the highest mean
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30 PTV Dmean. Given the relationships found between MLC margins and both the PTV coverage
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32 and HI metrics studied, the data was not found to be useful in determining the optimal MLC
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34 margins. The optimal CI results were observed to be with 0.0 mm MLC margins (1.18), although
35
the population showed no significant difference with -1.0 mm MLC margins (1.20). The optimal
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37 mean GI results were observed to be with -2.0 mm margins (2.99). However, in the population, -
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39 1.0 mm and 0.0 mm MLC margins were not significantly different than the optimal value. Both
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41 the mean liver Dmean and mean liver V20Gy results were optimal with 0.0 mm MLC margins with -
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43 1.0 mm margins exhibiting no significant statistical differences in the population.
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45 Given the known differences between the AAA and AXB algorithms in regions of high
46 heterogeneity, an impact on the optimal MLC margins utilizing AXB was expected. In the
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48 limited number of patients selected for this study, the mean amount of lung included as part of
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50 the PTV studied was 10.6%. In cases with greater PTV expansion or larger GTV which would
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52 intrinsically cause more involvement with the lung parenchyma, the disparities between
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54 algorithms may become more apparent.
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56 The studies performed by Ogata et al13 and Cardinale et al15 were important in
57 establishing guidelines in reference to which MLC margin resulted in optimal PTV and OAR
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59 results when planning SBRT of the liver. Both studies were performed using algorithms with
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4 limited dose model capabilities, with the potential to impact the appropriate MLC margins
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6 needed to provide optimal PTV and OAR treatment plan results. The current research findings
7
8 were analogous to those found by Ogata et al13 and Cardinale et al15 in studying optimal MLC
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10 margins in SBRT liver treatment. Ogata et al13 concluded the MLC margins of 0.0 mm and -1.0
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12 mm were found to provide optimal CI, GI, and liver tissue sparing. In the Cardinale et al15 study,
13
14
the results showed plans with a 0.0 mm MLC margin proved to provide the best liver sparing.
15 The statistical testing of the optimal MLC margins exhibited overall non-significance between
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17 the MLC margins as observed in CI, liver Dmean, and liver V20Gy metrics. However, during plan
18
19 evaluation the clinician would likely select the plan which would provide the optimal conformity
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21 and maximum OAR dose reduction.
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23 Conclusion
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25
Stereotactic body radiotherapy has been shown be safe and effective in the management
26 of primary liver cancers and liver metastases.1,2 Flattening filter free beams are favored in SBRT
27
28 because of the dramatic dose rate increase over FF beams which leads to decreased intra-fraction
29
30 motion and increased patient comfort with less time spent on the treatment table. Advanced
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32 calculation algorithms such as AXB have been shown to better model radiation doses as
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34 compared to AAA algorithm, particularly in regions with a high degree of tissue inhomogeneities
35
such as the dome of liver.8,9 The current study, as suggested by Rana,16 displayed an over-
36
37 estimation of PTV doses by the AAA algorithm in areas with tissues of a high degree of
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39 heterogeneity.
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41 The purpose of the current study was to determine acceptable 10 MV FFF beam MLC
42
43 margins in the SBRT of dome of the liver lesions using the AXB algorithm. While evaluating
44
45 effects of various uniform MLC margins using 10 MV FFF beams utilizing AXB algorithm in
46 SBRT of superior liver lesions near the dome, acceptable MLC margins were found to be -1.0
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48 mm and 0.0 mm. The current research findings mirror the results of Ogata et al13 identifying
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50 suitable FFF beam MLC margins in liver SBRT. The introduction of the AXB algorithm coupled
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52 with plans with heterogeneous PTV at the dome of the liver resulted in no difference in optimal
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54 SBRT 10MV FFF MLC margins, with results of the study accepting all null hypotheses.
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56 A limitation of this study was the wide range of PTV sizes and variance in the amount of
57 lung tissue included in them. The small population sample size was due to the limited number of
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59 patients in the department which fit the study criteria. Further studies are needed to describe the
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4 effects of both PTV size and amount of lung inclusion in PTV on the optimal FFF beam MLC
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6 margins using AXB algorithm. The results found in this study may be further refined by
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8 implementing asymmetric MLC margins.
9
10 Acknowledgements
11
12 The authors would like to thank Dr. David Reineke of the UW-La Crosse Statistical
13
14
Consulting Center for his assistance in statistical analysis and interpretation of statistical results
15 of the study. However, any errors of fact or interpretation remain the sole responsibility of the
16
17 authors.
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Figure 1

Figures

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

Figure 2

Figure 2. Optimized AXB plan mean PTV D99% (Gy) across all MLC margins. Green cells
represent the optimal level and the yellow shading is for MLC levels that are not significantly
different from the optimal for that response variable.
Figure 3

Figure 3. Optimized AXB plan mean PTV Dmean (Gy) across all MLC margins. Green cells
represent the optimal level and the yellow shading is for MLC levels that are not significantly
different from the optimal for that response variable.
Figure 4

Figure 4. Optimized AXB plan mean HI across all MLC margins. Green cells represent the
optimal level and the yellow shading is for MLC levels that are not significantly different from
the optimal for that response variable.
Figure 5

Figure 5. Optimized AXB plan mean CI across all MLC margins. Green cells represent the
optimal level and the yellow shading is for MLC levels that are not significantly different from
the optimal for that response variable.
Figure 6

Figure 6. Optimized AXB plan mean GI across all MLC margins. Green cells represent the
optimal level and the yellow shading is for MLC levels that are not significantly different from
the optimal for that response variable.
Figure 7

Figure 7. Optimized AXB plan mean Liver Dmean (Gy) across all MLC margins. Green cells
represent the optimal level and the yellow shading is for MLC levels that are not significantly
different from the optimal for that response variable.
Figure 8

Figure 8. Optimized AXB plan mean Liver V20Gy (cm3) across all MLC margins. Green cells
represent the optimal level and the yellow shading is for MLC levels that are not significantly
different from the optimal for that response variable.
Table 1

Tables

Table 1. Comparison between AAA and AXB plans using preset MUs from the AAA plans across all
uniform MLC margins.
MLC margin (mm) -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Mean
Optimized
37.70 40.15 42.98 45.29 46.56 47.27 47.68 48.05 48.28 44.89
AAA
Mean PTV AXB Preset
38.21 39.86 41.97 44.04 45.52 46.57 47.16 47.74 48.09 44.35
D99% (Gy) AAA MU
P-valuea 0.025 0.006 0.006 0.006 0.021 0.037 0.063 0.322 0.636
Optimized
50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00
AAA
Mean PTV AXB Preset
49.81 49.18 48.92 49.11 49.34 49.65 49.84 49.97 49.99 49.54
D95% (Gy) AAA MU
P-valuea 0.233 0.006 0.006 0.006 0.029 0.151 0.555 1.000 1.000
Optimized
84.48 72.89 65.50 60.27 57.42 56.19 55.41 54.81 54.41 62.38
AAA
Mean PTV AXB Preset
83.87 72.36 65.05 60.07 57.41 56.0 55.24 54.64 54.21 62.09
Dmean (Gy) AAA MU
P-valuea 0.012 0.012 0.012 0.119 0.160 0.108 0.108 0.108 0.108
a FDR-adjusted
Table 2

Table 2. The AXB plan results for PTV coverage across all uniform MLC margins studied.
Green cells represent the optimal level and the yellow shading is for MLC levels that are not
significantly different from the optimal for that response variable (P > 0.05).
MLC margin (mm) -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Mean
Mean PTV D99%
38.34 40.55 43.03 44.97 46.23 47.03 47.47 47.94 48.24 44.87
(Gy)
Standard Deviation 1.32 1.18 0.70 0.77 0.88 0.90 0.83 0.74 0.67

P-value 0b 0b 0b 0b .0112 .0902 .2732 .6812 -

Mean PTV Dmean
84.09 73.39 66.24 60.95 58.09 56.31 55.34 54.60 54.16 62.57
(Gy)
Standard Deviation 5.75 2.64 1.49 0.91 0.71 0.70 0.66 0.70 0.70

P-value - .4016 .0886 .0104 .0006 0b 0b 0b 0b

b
Significantly different from the optimal value in the population (P < 0.005)
Table 3

Table 3. The AXB plan results for plan quality indices across all uniform MLC margins studied.
Green cells represent the optimal level and the yellow shading is for MLC levels that are not
significantly different from the optimal for that response variable (P > 0.05).
MLC margin (mm) -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Mean
Mean HI 2.16 1.77 1.53 1.36 1.27 1.21 1.18 1.16 1.15 1.4
Standard Deviation 0.25 0.12 0.07 0.04 0.03 0.03 0.03 0.03 0.03
P-value 0c 0c 0c 0c .0040 .0626 .3292 .7482 -
Mean CI 1.44 1.29 1.20 1.18 1.20 1.26 1.32 1.39 1.48 1.3
Standard Deviation 0.21 0.13 0.09 0.10 0.11 0.12 0.15 0.16 0.19
P-value 0c .0514 .5954 - .6968 .1654 .0168 .0008 0c
Mean GI 3.02 2.99 3.01 3.09 3.22 3.36 3.50 3.71 3.83 3.3
Standard Deviation 0.22 0.25 0.25 0.23 0.26 0.33 0.43 0.57 0.54
P-value .8238 - .864 .4882 .1192 .0166 .0036 0c 0c
c
Significantly different from the optimal value in the population (P < 0.005)
Table 4

Table 4. The AXB plan results for liver OAR sparing across all uniform MLC margins studied.
Green cells represent the optimal level and the yellow shading is for MLC levels that are not
significantly different from the optimal for that response variable (P > 0.05).
MLC margin (mm) -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0 Mean
Mean Liver Dmean
6.09 5.70 5.47 5.41 5.54 5.78 6.04 6.36 6.69 5.90
(Gy)
Standard Deviation 3.14 3.03 2.91 2.87 2.91 3.01 3.09 3.23 3.35

P-value 0.436 .7064 .9046 - .8238 .6256 .4722 0.325 .2146

Mean Liver V20Gy
94.8 87.4 83.3 83.2 86.9 92.6 98.8 106.8 115.1 94.3
(cm3)

Standard Deviation 47.29 45.70 44.14 43.75 45.06 47.54 49.65 53.05 56.11

P-value .3552 .6812 0.959 - 0.758 .4616 .2376 .0986 .0480