1

Dosimetric Comparison of Stereotactic Radiosurgery for Multiple Brain Metastases:

Multiple-Isocenter Non-coplanar VMAT vs. CyberKnife
Authors: Sabrina Zeiler, B.S.R.T.(T), Karol Wynn, C.M.D, B.S.R.T.(T),Nishele Lenards, MS,
CMD, R.T. (R)(T), FAAMD, Ashley Hunzeker, MS, CMD

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

Abstract:
Introduction: The purpose of this study is to evaluate and compare dosimetric parameters and
efficiency of two stereotactic radiosurgery (SRS) modalities for multiple brain metastases:
CyberKnife and linear-accelerator (LINAC)-based volumetric modulated arc therapy (VMAT).
Case Description: Five SRS cases previously treated with CyberKnife, each with 2 to 3
intracranial target volumes, were retrospectively selected and re-planned using multipleisocenter, non-coplanar VMAT planning. Prescription doses were prescribed based on lesion
size. Dosimetric parameters including conformity index (CI), gradient index (GI), total 12 Gy
isodose volume (V12Gy), low-dose spillage (Dspill), and total procedure time were evaluated and
compared.
Conclusion:
Key words: Stereotactic Radiosurgery (SRS), Cyberknife, VMAT
Introduction
Over half of patients who develop intracranial metastases present with multiple lesions.1
Stereotactic radiosurgery is a widely utilized and highly effective treatment for metastatic
intracranial disease. There are many modalities and techniques for SRS treatment including
Gamma Knife (GK), CyberKnife, and, more recently, LINAC-based VMAT has been introduced.
Radiosurgery delivered with these systems allows for less invasive treatment of complex
intracranial targets.
The SRS treatment technique allows for large doses of radiation to be delivered to
defined-target volumes while sparing surrounding healthy tissue.1 Recent retrospective studies
have demonstrated the effectiveness of the SRS technique for treatment of multiple lesions.1,2
Single-isocenter planning of multiple intracranial lesions for SRS has become increasingly
popular because of the increased efficiency and marked reduction in treatment time that it can
provide.1 However, Roper et al3 found that slight rotational errors can compromise target

coverage when using a single-isocenter for multiple-target SRS procedures. For this reason, and
the meticulous imaging and adjustment protocols used in CyberKnife procedures, in this study,
each target was individually planned with a unique isocenter.
The LINAC-based VMAT technique has shown promise for decreasing treatment time
while maintaining target coverage and a steep-dose gradient within healthy tissue outside the
target volume. Recent studies have compared various dosimetric parameters of GK with VMAT
SRS, but very little research has been published evaluating and comparing dosimetric parameters
of Cyberknife and VMAT SRS treatments.4 This retrospective study seeks to compare the quality
of intracranial SRS using multiple-isocenter, non-coplanar LINAC-based VMAT and CyberKnife
by evaluating various dosimetric parameters commonly used to assess SRS plan quality.
Case Description
Patient Selection & Setup
Image data from 5 patients who were previously treated with single fraction intracranial
SRS for multiple intracranial lesions (i.e., 2 to 3 lesions) using CyberKnife were retrospectively
selected as reference candidates and re-planned using LINAC-based VMAT. Patient
identification numbers along with primary tumor site, number of intracranial targets, and target
volumes are listed in Table 1. The radiation oncologist discussed rationale for whole brain
radiation therapy (WBRT) versus SRS for the treatment of these targets and each patient opted
for SRS.
Patients were simulated in the head first supine position, lying on a foam pad. The head
was immobilized with a U-Frame thermoplastic mask with the appropriate head holder. A patient
specific foam head holder was occasionally employed to increase patient comfort and
immobilization. The mask holder was indexed to the table abutting the foam pad. High resolution
computed tomography (CT) scans were acquired for treatment planning. A Siemens Somotom
Sensation Open CT scanner was utilized and scans were acquired with a 1.0 mm slice thickness.
The scan range was from 3-5 cm superior to the vertex of the head and extended inferiorly to
mid-cervical spine. Additionally, high-quality magnetic resonance (MR) scans with 2.0 mm slice
thickness from a 1.5-T or 3.0-T unit were obtained to aid in target delineation. The scans
acquired were: T1 weighted axials without contrast, T2 axials and T2 Flair, and contrast
enhanced T1 axial, coronal, and sagittal MR scans.

Target Delineation and Contouring

Using the fusion software in Multiplan 5.1.2 (Accuray), the treatment planning CT and
MR scans were fused. Intracranial gross tumor volumes (GTVs) and the optic chiasm were
delineated and contoured by the referring neurosurgeon and verified by the attending radiation
oncologist. All organs at risk (OR) were contoured by the planning dosimetrist and subsequently
reviewed by the radiation oncologist. For Cyberknife planning, no margins were used for
treatment planning therefore no margins were used on the VMAT plans.
Treatment Planning
Prescription doses for each SRS target were determined based on lesion size using RTOG
9508. Prescription doses for each target volume are listed in Table 1. CyberKnife plans were
created for all patients using Multiplan treatment planning system (TPS) 5.1.2 (Accuray) and
treated with the CyberKnife VSI model. Align task and treatment parameters were defined after
contouring. The initial path selection (ie, 1path, shortpath, and even path) was determined by
target location, number of targets, and patient condition. The treatment parameter selections were
selected for each case. Patient specific parameters included: Iris or fixed collimator, number of
fractions, and tracking method. Appropriate collimator selection was determined based on target
diameter.
Each plan was optimized with the Sequential Optimization Algorithm. This planning
option uses a sequential step process to meet the clinical objectives defined by the planner.5 A
series of maximum dose constraints were set to the targets and dose volume constraints were
defined to the critical structures. The dose objectives were then defined to the targets to optimize
by minimum dose, optimal coverage, or dose volume lower limits (Figure 1). The planning
process continued until the best solution was found; as defined by the target dose conformity,
gradient and homogeneity indices, treatment time and critical structure doses. The plans were
calculated in high resolution utilizing the ray-tracing algorithm. Table 2 contains Cyberknife plan
parameters for each target.
For all brain Cyberknife SRS treatments 6D Skull tracking was utilized and setup images
were registered to the treatment planning DRRs (Figure 2 and 3). This tracking method is based
on a rigid registration of the bony anatomy from the digital reconstructed radiograph (DRR)
generated in the TPS. During treatment, x-ray images are acquired in real time to track variances

in the skull position from the DRR. The variations are calculated in three translations and three
rotations; the robot adjusted position to correct for positional changes.5
There are general guidelines followed for treatment planning with a single plan per target
for multi-lesion brain metastases with Multiplan. The goals are to avoid overlapping of beam
entrance points between plans, reduce the modulation factors, minimize treatment time and
achieve prescription goals. For targets in close proximity to each other, the 50% IDL is
monitored closely to assure these doses do not intersect in the plan summation. Additional
challenges include previous SRS and/or external beam radiation therapy (EBRT), adjacent
critical structures and patient performance status.
All cases were retrospectively re-planned using non-coplanar 6-MV flattening filter free
(FFF) VMAT using the Varian Eclipse TPS (Version 13) and were generated using Varian
Truebeam with 5 mm Millennium MLC system. The dose rate was set at 1400 cGy/min. Dose
was calculated for all plans using either Acuros XB or anisotropic algorithm (AAA) and a 1.0
mm grid resolution. Each target was inversely planned with a unique isocenter and 2 to 4 noncoplanar partial or complete arcs. Collimator angles and couch rotations were adjusted based on
optimal positioning for each target location, shape, and adjacent OR. Since multiple noncoplanar plans were created for each patient, couch rotations were not repeated in order to avoid
potential overlap of dose in normal tissue. Table 3 contains VMAT plan parameters for each
target.
For each target, 2 control rings (ie, an inner and outer ring) were created and utilized to
facilitate increased dose fall-off outside of the target in the optimization process. The inner rings
were expanded peripherally from each target and the outer rings were expanded an additional
distance from the periphery of the inner ring. Figure 4 illustrates the inner and outer control rings
with respect to the GTV. The ring expansions varied in diameter depending on the target size and
proximity to OR.
While dose-volume histogram (DVH) evaluation offers a direct visual analysis of
cumulative and quantitative information of dose to volume distribution for contoured structures,
researchers have suggested using data derived from DVH evaluation in calculations for CI and
GI to evaluate the quality of SRS treatment plans.6 Plan quality indices suggested by Radiation
Therapy Oncology Group (RTOG) and Paddick, including CIRTOG, CIPaddick, and GIPaddick were
utilized to compare CyberKnife and VMAT plan quality. The CIRTOG is defined as the ratio of

prescription isodose volumes, whereas CIPaddick is found through a combination of undertreatment

and overtreatment ratios (Equations 1 and 2).7 These indices allow for direct evaluation of dose
coverage across a target volume.6 The GIPaddick evaluates dose falloff outside of the target volume
through a ratio of the 50% isodose volume (PIV50%) to prescription isodose volume (PIV) as
shown in Equation 3. These indices are simple yet useful tools for evaluating dose conformity
and falloff and were utilized for assessment and comparison of the SRS plans for this study.7 The
indices and their equations are defined in Equations 1, 2, and 3.
CIRTOG = PIV/TV

(1)

CIPaddick=(TVPIV)2/(TVxPIV) (2)
GIPaddick= PIV50%/PIV

(3)

Development of radionecrosis has been associated with the total volume of normal brain
tissue, greater than 7.9cc, irradiated to 12 Gy (V12Gy) after intracranial radiation treatment.4,8,9
Therefore, it is an important factor to calculate when assessing SRS plan quality. For each
patient, CyberKnife and VMAT plan sums were utilized to calculate and compare the V12Gy.
The Dspill is used to evaluate an SRS plans ability to confine low isodose spread within
the vicinity of the target volume without extending into healthy brain tissue. In this study, this
measure of falloff gradient was evaluated based on total tissue DVH. The value for Dspill in each
plan was defined at the dose where the volume increase exceeded 2cc/cGy.4,10
Since VMAT offers the potential for improved efficiency through shorter treatment times,
overall procedure times were calculated or estimated for each patient. Overall CyberKnife setup
and treatment times were calculated based on estimated and recorded data. However, VMAT
procedure times were calculated based on estimated setup time and imaging procedures per
isocenter as well as actual treatment time based on recorded data from performing each treatment
plan on the LINAC. Overall procedure time included setup time, imaging procedures, and actual
treatment time.
The three-dimensional (3D) dose matrices for both the CyberKnife plans and VMAT plan
sums were exported to a third party system for evaluation (Velocity, Version 3.1) in order to
directly compare the plans from the two different TPSs. Analyses were performed to compare the
quality of each Cyberknife plan versus VMAT based on the aforementioned dosimetric
parameters including CI, GI, normal tissue V12Gy, Dspill, and overall procedure time.

Plan Evaluation & Analysis

Data processing and analyses were performed for each SRS plan and composite plan for
each patient.
Insert results paragraph leading into the Discussion of planning results & challenges
The treatment planning procedure for the Cyberknife cases incorporated the previously
discussed guidelines and processes. Additionally, there were patient specific circumstances that
required special attention and individual challenges. Patient 1 presented with two lesions on
opposite sides of the brain, a 17mm right parietal lesion and a 6mm left thalamic lesion. The
thalamic volume of 0.083cc had good conformality, but a poor gradient index due to limiting
beams through previously treated SRS targets. There were several specific challenges faced with
Cyberknife planning for Patient 2 and 3. Patient 2 had multiple targets on the both sides of the
brain. Since the robot can and will deliver treatment beams in all planes, the optimization
constraints were set such that each plan limits beams from directly entering through the other
targets. This limitation, as well as those set on beam entrance for the oral cavity and lenses, does
affect the conformality. For Patient 3, the plan for the right temporal lesion was somewhat
difficult due to the proximity of the target to the skin, cochlea and brainstem. Additionally, the
Cyberknife beams were set to avoid bilateral lenses and the oral cavity. Additionally, this
patients total treatment time was longer due to the patients inability to stay still. This motion
prompts in-room repositioning and increases the number and frequency of image acquisitions,
which leads to increased overall treatment time. Patient 4s left temporal lesion presented
difficulty with the brain V12 constraint, due to its size of 4.1 cc and location adjacent to the left
optic apparatus.
As with Cyberknife, when planning multiple-isocenter, one-plan-per-target using noncoplanar VMAT, it is important to avoid overlap by using different VMAT geometry for every
arc. This created various limitations and challenges when planning. To be continued when
VMAT results are acquired.
Cyberknife procedure times were evaluated based on documented fraction delivery
reports from the Accuray system. The setup time was averaged between all patient procedures at
5 minutes because of variable wait-time between patient setup and physician arrival for image
approval. This setup time includes patient setup on the treatment table, mask placement and the
first set of images and alignment to DRRs. Once the physician and physicist approve setup

images treatment can be initiated. The imaging protocol was set for images every 30 to 45
seconds and the number of image sets per plan are documented. The imaging and treatment times
are combined in the report as delivery time. Additionally, most plans utilize two collimators; in
these cases the collimator change time is recorded. Table 4 contains procedure times from
fraction delivery reports for each target and patient.
VMAT procedure times were estimated as previously discussed and are shown in Table 5.
Duration of LINAC-based VMAT patient setup and imaging procedures were estimated based on
actual setup and imaging times of 3 SRS procedures. Patient setup time took an estimated 3.6
minutes. Initial orthogonal kV imaging, evaluation, and adjustments were completed in an
average of 2.4 minutes and subsequent cone-beam CT (CBCT), evaluation, and adjustments took
an average of 4.8 minutes to complete. Thus, the total estimated imaging procedure time for a
single VMAT plan was 7.2 minutes. This estimated imaging time was applied for each individual
plan as separate imaging would be required for each new isocenter. Actual beam on times were
found by running plans for each VMAT plan on the LINAC. Table 5 contains the procedure
times for estimated patient setup time and imaging procedures, and actual beam on time for each
plan, in addition to total estimated procedure time for each target and patient.
Conclusion

References
1. Nath SK, Lawson JD, Simpson DR, et al. Single-isocenter frameless intensity-modulated
stereotactic radiosurgery for simultaneous treatment of multiple brain metastases: Clinical
experience. Int J Radiat Oncol Biol Phys. 2010;78(1):91-97.
http://dx.doi.org/10.1016/j.ijrobp.2009.07.1726
2. Park SH, Hwang SK, Kang DH, et al. Gamma knife radiosurgery for multiple brain metastases
from lung cancer. J Clin Neurosci. 2009;16:626-629.
3. Roper J, Chanyavanich V, Betzel G, Switchenko J, Dhabaan A. Single-isocenter multiple-target
stereotactic radiosurgery: Risk of compromised coverage. Int J Radiat Oncol Biol Phys.
2015;93(3):520-546. http://dx.doi.org/10.1016/j.ijrobp.2015.07.2262
4. Liu H, Andrews DW, Evans JJ, et al. Plan quality and treatment efficiency for radiosurgery to
multiple brain metastases: Non-Coplanar RapidArc vs. gamma knife. Front Oncol. 2016;6(26):18. http://dx.doi.org/10.3389/fronc.2016.00026
5. Accuray Corporation. CyberKnife Robotic Radiosurgery System. Treatment Planning Manual.
Version 5.0x, 2014.
6. Lomox NJ, Scheib SG. Quantifying the degree of conformity in radiosurgery treatment planning.
Int J Radiat Oncol Biol Phys. 2003;55(5):1409-1419. http://dx.doi.org/10.1016/S03603016(02)04599-6
7. Paddick I, Lippitz B. A simple dose gradient measurement tool to complement the conformity
index. J Neurosurg. 2006;105(suppl 7):194-201.
http://thejns.org/doi/abs/10.3171/sup.2006.105.7.194
8. Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Brenemen JC. Irradiated volume
as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat
Oncol Biol Phys. 2010;77(4):996-1001. http://dx.doi.org/10.1016/j.ijrobp.2009.06.006
9. Enachescu C, Udrescu C. Brain metastases in malignant melanoma- treatment options and
recommendations. Romanian J Clin Experiment Derm. 2014;1(1):52-61.
10. Liu H, Andrews D, Werner-Wasik M, Yu Y, Dicker A, Shi W. Compare low dose spilling between
VMAT and gamma knife radiosurgery for multiple brain metastases. Presented at: The
Radiosurgery Society SRS/SBRT Scientific Meeting. May 7-10, 2014; Minneapolis, Minnesota.
Figures

Figure 1. Sequential optimization window for Cyberknife treatment planning. The upper table
parameters define hard constraints for the optimizer. The dose objective section defines the
prescription parameters to the targets.

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Figure 2. 6D skull tracking setup DRRs used to track the patients head position.

Figure 3. Initial setup images registered to the treatment planning DRRs.

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Figure 4. Inner and outer control rings in relation to the GTV.

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Tables
Table 1. Patient identification number, target volumes,
and prescription dose for each intracranial target.
Patient and
Target
Prescription
Targets
Volume (cc)
Dose
Patient 1
Thalamus_L
0.083
18Gy
Parietal_R
2.44
21Gy
Patient 2
Frontal _L
0.524
20Gy
Occipital_R
0.470
20Gy
Occipital_L
1.52
20Gy
Patient 3
Temporal_R
2.89
20Gy
Frontal_L
0.032
20Gy
Patient 4
Frontal_L
0.769
18Gy
Temporal _L
4.1
18Gy
Patient 5
Cerebellar_L
3.85
18Gy
Temporal_R
1.5
20Gy
Temporal_L
0.228
20Gy
Table 2. Cyberknife treatment plan parameters for Patients 1-5.
Patient
Patient 1
Thalamus_L
Parietal_R
Patient 2
Frontal _L
Occipital_R
Occipital_L
Patient 3
Temporal_RF
rontal_L
Patient 4
Frontal_L
Temporal _L
Patient 5
Cerebellar_L

Cone Size

CI

GI

nCi

V12 (cc)

5mm & 7.5mm

10mm & 15mm

1.14
1.10

6.4
3.3

1.20
1.15

0.323
7.2

5mm & 10mm

7.5mm & 10mm
7.5mm &15mm

1.29
1.41
1.40

2.5

3.3

1.29
1.41
1.40

10mm
5mm

1.12
1.72

2.8
7.5

1.1
1.77

6.9
0.273

12.5mm
10mm & 12mm

1.27
1.11

3.2
2.7

1.33
1.15

1.97
7.8

7.5mm & 10mm

1.07

2.5

1.13

7.9

5.5

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Temporal_R
Temporal_L

10mm & 15mm

7.5mm & 10mm

1.14
1.14

3.1
4.3

1.18
1.17

4.1
1.02

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Setup
Time
(estimated)

Image
Acquisition
Time

Treatment
Delivery
Time

Total
Procedure
Time

Table 3. VMAT treatment

Patient and
plan parameters for
Targets
Patients 1-5.
Patient 1
Patient and Targets
VMAT
CI
GI
nCi
V12
Thalamus_L
5:00
16:44
1:30
23:14
Geometry
(cc)
Parietal_R
5:00
29:21
1:30
35:51
Patient 1
Patient 2
Thalamus_L
Frontal _L
5:00
18:20
1:30
23:20
Parietal_R
Occipital_R
5:00
36:15
1:30
42:45
Patient 2
Occipital_L
37:01
1:30
45:01
Frontal _L 5:00
Patient 3
Occipital_R
Temporal_R
5:00
18:35
0
23:35
Treatment
Cone
Total
Occipital_L Setup
Frontal_L
5:00
41:16
0
46:16
Patient
3
Patient
and
Time
Delivery
Image
Exchange Procedure
Patient 4
Temporal_R
Targets
(estimated)
Time
Acquisitions
Time
Time
Frontal_L
5:00
35:01
0
40:01
Patient 1 Frontal_L
Temporal
5:00
14:41
046
19:41
Thalamus_L
5:00
16:44
1:30
23:14
Patient _L
4
Patient 5
Parietal_R
5:00
29:21
78
1:30
35:51
Frontal_L
Cerebellar_L
18:25
1:30
24:55
Patient
2 Temporal _L5:00
Temporal_R
5:00
22:39
1:30
28:09
Frontal
_L5
5:00
18:20
82
1:30
23:20
Patient
Temporal_L
5:00
44:08
1:30
50:38
Occipital_R
36:15
102
1:30
42:45
Cerebellar_L 5:00
Occipital_L
37:01
128
1:30
45:01
Temporal_R 5:00
Patient 3 Temporal_L
Temporal_R
5:00
18:35
88
0
23:35
Frontal_L
5:00
41:16
148
0
46:16
PatientTable
4 4. Estimated overall procedure time for Cyberknife based on setup time, imaging
time, and beam on time.
recorded in minutes:seconds.
Frontal_L
5:00 Times are
35:01
108
0
40:01
Table 5. Estimated overall procedure time for VMAT based on setup time,
Temporal _L
5:00
14:41
62
0
19:41
imaging time, and beam on time. Times are recorded in minutes:seconds.
Patient 5
Cerebellar_L
5:00
18:25
48
1:30
24:55
Temporal_R
5:00
22:39
56
1:30
28:09
Temporal_L
5:00
44:08
104
1:30
50:38

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Table 6. Comparison of Cyberknife and VMAT CI with target size for reference.
Patient and
Cyberknife
Targets
Target Size (cc)
CI
VMAT CI
Patient 1
Thalamus_L
0.083
Parietal_R
2.44
Patient 2
Frontal _L
0.524
Occipital_R
0.470
Occipital_L
1.52
Patient 3
Temporal_R
2.89
Frontal_L
0.032
Patient 4
Frontal_L
0.769
Temporal _L
4.1
Patient 5
Cerebellar_L
3.85
Temporal_R
1.5
Temporal_L
0.228
Table 7. Comparison of Cyberknife and VMAT GI with target size for reference.
Patient and
Targets
Patient 1
Thalamus_L
Parietal_R
Patient 2
Frontal _L
Occipital_R
Occipital_L
Patient 3
Temporal_R
Frontal_L
Patient 4

Target Size (cc)

0.083
2.44
0.524
0.470
1.52
2.89
0.032

Cyberknife
GI

VMAT GI

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Frontal_L
Temporal _L
Patient 5
Cerebellar_L
Temporal_R
Temporal_L

0.769
4.1
3.85
1.5
0.228

Table 8. Comparison of Dspill between Cyberknife and

VMAT plans for each patients plan sum.
Patient
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5

Cyberknife Dspill

VMAT Dspill