1

Evaluation of multiple VMAT planning techniques for hippocampal sparing whole brain
radiotherapy

Kearla Bentz, BAS, RT(R)(T); Kristen Eberhard, BS, RT(R)(T); Allison Wright, BS, RT(T);
Nishele Lenards, PhD, CMD, RT(R)(T), FAAMD; Ashley Hunzeker, MS, CMD and Matt
Tobler, CMD, RT(T), FAAMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI

Abstract
Achieving dose constraints in the hippocampus avoidance CC001 phase III trial presented by
NRG Oncology (NRG) can result in unwanted areas of increased dose to the normal brain and
organs at risk (OAR). The problem is that high dose received by the hippocampi can cause
radiation-induced side effects such as decreased neurocognitive function in patients. The purpose
of this study was to evaluate 3 volumetric modulated arc therapy (VMAT) hippocampal sparing
(HS) whole-brain radiation therapy (WBRT) techniques, each designed to simultaneously
decrease dose to the hippocampi, limit areas of increased dose, and maintain planning target
volume (PTV) coverage as required by the NRG-CC001 dose constraints. Researchers tested the
hypotheses that VMAT planning techniques “A” (H1A), “B” (H3A), and “C” (H5A) will achieve a
mean (n=10) maximum dose (Dmax) to the hippocampi < 16.0 Gy and techniques “A” (H2A), “B”
(H4A), and “C” (H6A) will achieve a mean (n=10) maximum dose to 2% (D2%) of the PTV <
115% of the prescribed dose (34.50 Gy), while maintaining PTV coverage and meeting the
NRG-CC001 dose constraints for the optic structures. Ten HS-WBRT patients were selected and
planned with the 3 techniques using constraints from the NRG-CC001 protocol. For the mean
(n=10) hippocampi Dmax dose, the results were significant for techniques “A”, “B”, and “C”;
therefore, researchers rejected the null hypotheses for all 3 techniques. For the mean PTV D 2%,
the results were P=0.421987 for technique “A”, P=0.215887 for “B”, and P=0.4197 for “C” and
not statistically significant; therefore, researchers failed to reject the null hypotheses for all 3
techniques.
Keywords: HS-WBRT, VMAT, NRG-CC001, Hippocampus, Dmax, D2%
Introduction
Brain metastases is the most common form of brain cancer.1 The incidence of brain
metastases in the United States has been estimated to be around 70,000 to 400,000 newly
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diagnosed cases per year.2 Metastatic brain cancer is roughly 10 times more common than
primary malignant brain cancer, and about 10% to 40% of patients with solid tumors will
develop brain metastases.2 Whole-brain radiation therapy (WBRT) has been a standard palliative
radiotherapy treatment option for decades for patients with multiple brain metastases. 1,3
Developing brain metastases is a risk for patients with many different tumor types, including
small cell lung cancer (SCLC) and prophylactic cranial irradiation (PCI) may be recommended
to reduce this risk.4 Previous WBRT and PCI planning techniques have provided sufficient
coverage of the whole brain but have not been beneficial in reducing doses to organs at risk
(OAR) in the brain such as the hippocampi, optic chiasm, and optic nerves.
The hippocampus is a radiosensitive bundle of neural stem cells that is involved with
learning, memory, emotion, motor control, and endocrine regulation.1,5,6 The hippocampi are
shaped like a seahorse and are located in the medial temporal lobe of the brain, with one on the
right and one on the left side of the brain.5 Radiation can damage the hippocampi and lead to
adverse neurocognitive effects, as observed in traditional WBRT.3 Radiation-induced toxicities
from WBRT and PCI have been attributed to hippocampi damage, which has led to impairment
in cognitive function and a decreased quality of life.1,4 Redmond et al7 demonstrated that there is
a significant dose-response relationship between increased maximum dose to the hippocampi and
short-term memory deterioration.1 Therefore, it is believed that sparing of this region in WBRT
and PCI treatments may preserve cognitive function. Unfortunately, because of its central
location within the brain and unique shape, sparing the hippocampi is a challenge.4,5
Advancements in radiation therapy technology, such as multi-leaf collimators (MLCs)
and computer-controlled delivery systems, have allowed development of new treatment
alternatives for WBRT including intensity modulated radiation therapy (IMRT) and volumetric
modulated arc radiotherapy (VMAT). These new treatment options have shown comparable dose
coverage of the whole brain with lower dose to OAR and have enabled hippocampal sparing
(HS)-WBRT VMAT planning.6 These plans are used to reduce the radiation dose to the
hippocampi and other radiosensitive organs near the brain, including the optic chiasm and optic
nerves. The Radiation Therapy Oncology Group (RTOG) 0933 phase II study defined strict
target coverage and dose constraints to assess the effects of HS-WBRT. Researchers
demonstrated that the use of IMRT or VMAT reduced dose to the hippocampi and optic
structures. This resulted in less neurocognitive toxicity and vision deterioration. Results also
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showed that patients’ memory, recall, and quality of life at subsequent follow-up appointments
were better in comparison to historical WBRT treatments.3,8,9
A team of researchers from the National Surgical Adjuvant Breast and Bowel Project
(NSABP), the RTOG, and the Gynecologic Oncology Group (GOG), collaboratively known as
NRG Oncology (NRG), initiated the hippocampus avoidance CC001 phase III trial. Researchers
discovered that reducing hippocampal radiation dose along with adding a cognition-enhancing
medication had similar positive results in reduced cognitive toxicity at follow-up appointments 4
to 6 months after HS-WBRT.1,5 Tighter dose constraints may be beneficial because of the steep
dose-response relationship between radiation dose to the hippocampi and cognitive decline. 7
Incorporation of complex IMRT techniques utilized for this protocol not only allowed for dose
reduction to the hippocampi, but provided the treatment planner with the added advantage of
reducing dose to the optic structures.
Hippocampal sparing WBRT treatment planning can be labor-intensive. Meeting the
hippocampus dose constraint in the NRG-CC001 protocol can also result in unwanted areas of
increased dose to the normal brain and OAR which can result in radiation-induced side effects. 10
The problem is that the high dose received by the hippocampi can cause radiation-induced side
effects such as decreased neurocognitive function in patients. The purpose of this study was to
evaluate 3 VMAT HS-WBRT techniques, each designed to simultaneously decrease dose to the
hippocampi, limit areas of increased dose, and maintain planning target volume (PTV) coverage
as required by the NRG-CC001 dose constraints. Researchers tested the hypotheses that VMAT
planning techniques “A”, “B”, and “C” will achieve a mean (n=10) maximum dose (Dmax) to the
hippocampi < 16.0 Gy (H1A, H3A, and H5A, respectively) and a mean (n=10) maximum dose to
2% (D2%) within the PTV < 115% of the prescribed dose (H2A, H4A, and H6A, respectively),
while maintaining PTV coverage and NRG-CC001 dose constraints for the optic structures.
Materials and Methods
Patient Selection and Setup
For this retrospective study, 10 patients were selected, and their computed tomography
(CT) planning scans were used for evaluation. Every patient included in this study was treated at
one facility and prescribed HS-WBRT using VMAT planning for either brain metastases or PCI.
All patients underwent a CT simulation in the supine, head-first position using a thermoplastic
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head mask. The mask ensured reproducibility with minimal patient movement during treatment
(Figure 1).
Contouring
The contours included in this study followed the NRG-CC001 protocol constraint
requirements (Table 1).11 The OAR contoured were the hippocampi, optic chiasm, and the right
and left optic nerves. The hippocampi were delineated manually by one radiation oncologist. An
additional avoidance structure was created by three-dimensionally expanding the hippocampi
volume by 5.0 mm, following the NRG-CC001 protocol.12 The optic structures and PTV of each
treatment planning scan were auto-contoured at one facility and approved by one radiation
oncologist. These methods were used to reduce the variability in contoured structures. The PTV
consisted of the entire brain volume minus the optic chiasm, optic nerves, and the hippocampus
avoidance region.
Treatment Planning
All treatment planning was done by one researcher using the Eclipse treatment planning
system (TPS). The prescription dose was 30 Gy in 10 fractions, treated once daily. The algorithm
used for dose calculation was the anisotropic analytical algorithm (AAA) version 16.1.0. All HS-
WBRT VMAT plans utilized the Varian TrueBeam STX with high-definition MLCs (HD-
MLCs) including 32 central 2.5 mm width and 28 outer 5.0 mm width MLCs. The isocenter for
all plans was placed near the center of the brain. Each plan utilized 6 MV flattening filter-free
(FFF) beams.
Three HS-WBRT planning techniques were compared in this research study. These
techniques have been used by medical dosimetrists at 3 different cancer centers. Each plan had a
unique arrangement of beam angles and field designs (Table 2). The first VMAT HS-WBRT
technique “A” used 2 full arcs with fields covering the entire brain and 2 sagittal arcs that used
split-x technique separating the brain into left and right portions (Figure 2). The second HS-
WBRT VMAT planning technique “B” used 2 full arcs with split-x technique that separated the
brain superiorly and inferiorly and 2 sagittal arcs with split-x technique that separated the brain
into left and right portions (Figure 3). The VMAT planning technique “C” used 4 full arcs and a
sagittal arc with fields covering the entire brain (Figure 4).
A PTV optimization structure was created with a 5.0 mm outer margin from the PTV.
This structure was created to help with PTV coverage in the optimizer. It was cropped out of the
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hippocampus avoidance region and given an upper and lower objective, with the upper limit
slightly higher than the prescription and the lower limit < 33.0 Gy. These objectives were given
the highest priority unless priority adjustments were required to preserve hippocampus dose
constraints. Additional contours separating the brain into upper, middle, and lower portions were
created for optimization purposes and used as targets to help with volume coverage and reducing
areas of increase dose. The hippocampus was given 2 upper objectives, dose to 100% (D100%) <
9.0 Gy and Dmax < 16.0 Gy, and this structure’s objectives were given the second highest
priorities. Finally, all the remaining OAR were given upper objectives of Dmax < 30.0 Gy. The
researcher completed the optimization process for each planning technique as needed to obtain
passing or variation acceptable NRG-CC001 optic dose constraints while lowering the dose to
the hippocampi and minimizing areas of increased dose within the brain.
Plan Comparison
The 3 VMAT plans were compared using the previously mentioned table of NRG-CC001
protocol’s constraints (Table 1). Each plan was normalized so that 95% of the PTV was
receiving the prescription dose of 30.0 Gy. The evaluated metrics included dose statistics of the
hippocampi Dmax and D100%, optic structures Dmax, and the maximum dose to D2% of the PTV. The
hippocampi were assessed based on goal of Dmax < 16.0 Gy, although NRG-CC001 variation
acceptable limit is ≤ 17.0 Gy. Furthermore, the PTV D2% was compared between planning
techniques with the goal < 115% (34.50 Gy), although NRG-CC001 protocol variation
acceptable limit is ≤ 133% (40.0 Gy).
Statistical Analysis
The data from each planning technique was statistically analyzed for the evaluated
metrics including the mean (n=10) hippocampi Dmax and mean PTV D2%. A Kolmogorov-
Smirnov test was done to test for normality. Due to the sample size, variables, and non-
parametric data, a single sample t-test was performed for each of the 3 VMAT HS-WBRT
planning techniques. This test compared the Dmax and D2% mean results for each planning
technique to the objective values using a significance value of P < 0.1.
Results
Planning Technique “A”
The hippocampi Dmax for VMAT planning technique “A” ranged from a minimum of
13.86 Gy to a maximum of 16.60 Gy. For technique “A” the mean (n=10) hippocampi Dmax was
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15.10. The data for the hippocampi Dmax was input into the t-test and resulted in a significance
value of P=0.005258. The results for decreasing the Dmax to the hippocampi to < 16.0 Gy were
significant for planning technique “A”; therefore, researchers rejected the null hypothesis (H1 0).
The PTV D2% for planning technique “A” ranged from a minimum of 32.17 Gy to a
maximum of 37.09 Gy with a mean of 115.37% (34.61 Gy). The data for the mean (n=10) PTV
D2% for technique “A” was input into the t-test and resulted in a significance value of
P=0.421984. The results for reducing the PTV D2% to < 115% (34.50 Gy) were insignificant;
therefore, researchers failed to reject the null hypothesis (H20).
Planning Technique “B”
The hippocampi Dmax for VMAT planning technique “B” ranged from a minimum of
11.81 Gy to a maximum of 15.44 Gy. For technique “B” the mean (n=10) hippocampi Dmax was
14.19 Gy. The data for the hippocampi Dmax was input into the t-test and resulted in a
significance value of P=0.000341. The results for decreasing the hippocampi Dmax to < 16.0 Gy
were significant for planning technique “B”; therefore, researchers rejected the null hypothesis
(H30).
The PTV D2% for planning technique “B” ranged from a minimum of 32.67 Gy to a
maximum of 38.66 Gy with a mean of 113.37% (34.01 Gy). The data for the mean (n=10) PTV
D2% for technique “B” was input into the t-test and resulted in a significance value of
P=0.215887. The results for reducing the PTV D2% to < 115% (34.50 Gy) were insignificant;
therefore, researchers failed to reject the null hypothesis (H40).
Planning Technique “C”
The hippocampi Dmax for VMAT planning technique “C” ranged from a minimum of
12.02 Gy to a maximum of 16.34 Gy. For technique “C” the mean (n=10) hippocampi Dmax was
15.18 Gy. The data for the hippocampi Dmax was input into the t-test and resulted in a
significance value of P=0.031788. The results for decreasing the hippocampi Dmax to < 16.0 Gy
were significant for planning technique “C”; therefore, researchers rejected the null hypothesis
(H50).
The PTV D2% for planning technique “C” ranged from a minimum of 32.19 Gy to a
maximum of 37.63 Gy with a mean of 115.4% (34.62 Gy). The data for the mean (n=10) PTV
D2% for technique “C” was input into the t-test and resulted in a significance value of P=0.4197.
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The results for reducing the PTV D2% to < 115% (34.50 Gy) were insignificant; therefore,
researchers failed to reject the null hypothesis (H60).
Discussion
Advancements in radiation therapy technologies and complex planning techniques have
allowed dose reduction to OAR, such as the hippocampi, without compromising PTV coverage
in WBRT. Brown et al12 assessed the effects of HS-WBRT and have demonstrated that VMAT
planning could reduce hippocampal dose and the associated neurocognitive toxicity. Tighter
constraints could be beneficial because of the established relationship between bilateral
hippocampi maximum dose and short-term memory deterioration, even with patients who have
met protocol hippocampal constraints.7 In NRG-CC001, Dmax of 14.0 Gy and 16.0 Gy were
associated with a 10% and 25% risk of memory deterioration after 6 months.1 In the present
study of 3 HS-WBRT VMAT planning techniques using 10 patient CT data sets, the hippocampi
Dmax of < 16 Gy was achievable in 27 of the 30 treatment plans. The mean (n=10) hippocampi
Dmax for the 3 planning techniques ranged from 14.19 to 15.18 Gy, not significantly lower than 16
Gy. Although it would be beneficial to decrease the Dmax of the hippocampi further, further
reduction in dose to the hippocampi could negatively impact dosimetric plan quality due to the
central location.
Additionally, radiation toxicities can occur from increased radiation dose to the brain or
OAR from dose heterogeneities or areas of increased dose. The incidence and severity of the
toxicities are dose and volume dependent.14 Therefore, it is important to attempt to decrease areas
of increased dose and unnecessary dose to OAR. The NRG-CC001 protocol established set
constraints for the maximum dose to OAR and the treatment volume. However, the PTV D 2%
variation acceptable limit allows ≤ 133% (40.0 Gy) and ≤ 125% (37.5 Gy) for the maximum
dose to the optic structures. Since vision deterioration has been an issue with WBRT and
increased dose to the brain can cause functional decline, researchers in the current study set the
maximum dose limits to ≤ 30.0 Gy for the optic structures and attempted to achieve < 115%
(34.50 Gy) for the PTV D2%.4,5 The mean dose for each NRG-CC001 constraint metric was
calculated (Table 5). The mean dose measurements from Table 5 showed that the OAR Dmax
constraints were on average around 30 Gy and the PTV D2% around 115% (34.5 Gy) for all 3 HS-
WBRT plans. In this study, the D2% < 34.5 Gy was achieved in 20 of 30 patient plans. Of the 30
total plans created, only 10 met all NRG-CC001 protocol requirements with the remaining plans
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containing at least 1 constraint in the variation acceptable dose limit (Table 6). The results from
this study imply that the NRG-CC-001 protocol constraints are achievable using the 3 VMAT
planning techniques. All planning techniques were also successful for decreasing the hippocampi
Dmax to < 16.0 Gy, although, they were not statistically significant in further reducing the PTV
D2% to < 115% (34.50 Gy).
Overall, planning technique “B” was determined to be the most promising for decreasing
both the hippocampi Dmax and the PTV D2% dose while maintaining PTV coverage and NRG-
CC001 dose constraints. All the treatment plans using technique “B” resulted in < 16.0 Gy for
the Dmax to the hippocampi. Technique “B” also resulted in 80% of the plans with D2% within the
PTV < 115% (34.50 Gy). The promising results of planning technique “B” may be attributed to
utilization of 4 arcs with partial field split-x technique. Large radiation fields require a wide jaw
opening in which substantial low dose volume to the hippocampus can occur due to suboptimal
MLC movements.15 In reducing the size of the jaws for each field, the MLCs are able to
modulate better because their distance of travel is shorter. This could enable the MLCs to block
the hippocampi and other OAR more efficiently throughout each arc.
Conclusion
Hippocampal sparing WBRT treatment planning can be labor-intensive. Achieving the
hippocampus dose constraint in the NRG-CC001 protocol can also result in unwanted areas of
increased dose to the normal brain and OAR which can result in radiation-induced side effects. 10
The problem is that increased dose to the hippocampi can cause radiation-induced side effects
such as decreased neurocognitive function in patients. The purpose of this study was to evaluate
3 VMAT HS-WBRT techniques, each designed to simultaneously decrease dose to the
hippocampi, limit areas of increased dose, and maintain PTV coverage as required by the NRG-
CC001 dose constraints. Researchers tested the hypotheses that VMAT planning techniques “A”,
“B”, and “C” will achieve a mean (n=10) maximum dose (Dmax) to the hippocampi < 16.0 Gy
(H1A, H3A, and H5A, respectively) and a mean (n=10) maximum dose to 2% (D2%) within the
PTV < 115% of the prescribed dose (H2A, H4A, and H6A, respectively), while maintaining PTV
coverage and NRG-CC001 dose constraints for the optic structures. For the mean (n=10)
hippocampi Dmax dose, the results were significant for techniques “A”, “B”, and “C”; therefore,
researchers rejected the null hypotheses for all 3 techniques. For the mean (n=10) PTV D2%, the
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results were not statistically significant for techniques “A”, “B”, and C”; therefore, researchers
failed to reject the null hypotheses for all 3 techniques.
One of the limitations of this study was that data sets were collected from a single
institution using the same treatment planning system and algorithm. Although this creates
consistency within treatment planning and reduces variables, the results of this study may
contradict research using a different TPS or algorithm. Another limitation included the small
population of HS-WBRT patient data sets used (n=10) to evaluate the 3 planning techniques.
Future research should include a larger population of patient data sets.
Acknowledgments
The authors would like to thank Dr. Douglas Baumann of the Statistical Consulting
Center at the University of Wisconsin La Crosse for assistance with analysis and interpretation of
data. However, any errors of fact or interpretation remain the sole responsibility of the authors.
The authors would also like to thank Kevin Jacobson, CMD at Billings Clinic Cancer Center;
Ryan Pohl, CMD and Doug Kivi, CMD at St. Luke’s Cancer Center; and Jeff Whitmarsh, CMD
at OU Stephenson Cancer Center for assisting with HS-WBRT planning and optimization
techniques.
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References
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version 2 – how far can we reduce dose? Med Dosim. 2022;47:258-263.
https://doi.org/10.1016/j.meddos.2022.04.003
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disease. Neurol-Oncol. 2021;23(9):1447-1456. https://doi.org/10.1093/neuonc/noab101
3. Krayenbuehl J, Di Martino M, Guckenberger M, et al. Improved plan quality with automated
radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG
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4. Crockett C, Belderbos J, Levy A, McDonald F, Le Péchoux C, Faivre-Finn C. Prophylactic
cranial irradiation (PCI), hippocampal avoidance (HA) whole brain radiotherapy (WBRT)
and stereotactic radiosurgery (SRS) in small cell lung cancer (SCLC): where do we stand?
Lung Cancer. 2021;162:96-105. https://doi.org/10.1016/j.lungcan.2021.10.016
5. Sprowls CJ, Shah AP, Kelly P, et al. Whole brain radiotherapy with hippocampal sparing
using Varian HyperArc. Med Dosim. 2021;46:264-268.
https://doi.org/10.1016/j.meddos.2021.02.007
6. Kazda T, Vrzal M, Prochazka T, et al. Left hippocampus sparing whole brain radiotherapy
(WBRT): a planning study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.
2017;161(4):397-402. https://doi.org/10.5507/bp.2017.031
7. Redmond KJ, Grim J, Robinson CG, et al. Steep dose-response relationship between
maximum hippocampal dose and memory deficits following hippocampal avoidance whole
brain radiation therapy (HA-WBRT) for brain metastases: a secondary analysis of
NRG/RTOG 0933. Int J Radiat Oncol. 2020;18(3)S176.
https://doi.org/10.1016/j.ijrobp.2020.07.956
8. Shang W, Yao H, Sun Y, et al. Preventive effect of hippocampal sparing on cognitive
dysfunction of patients undergoing whole-brain radiotherapy and imaging assessment of
hippocampal volume changes. Biomed Res Int. April 5,2022;2022:1-10.
https://doi.org/10.1155/2022/4267673
9. Sood S, Pokhrel D, McClinton C, et al. Volumetric-modulated arc therapy (VMAT) for
whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to
organs at risk. Med Dosim. 2017;42:375-383. https://doi.org/10.1016/j.meddos.2017.07.005
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10. Pokhrel D, Sood S, McClinton C, et al. Treatment planning strategy for whole-brain
radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain
metastases using intensity-modulated arc therapy. Med Dosim. 2016;41(4)315-322.
https://doi.org/10.1016/j.meddos.2016.08.001
11. NRG Oncology. NRG-CC001: a randomized phase III trial of memantine and whole-brain
radiotherapy with or without hippocampal avoidance in patients with brain metastases.
September 26, 2017. Accessed July 6, 2023.
https://classic.clinicaltrials.gov/ProvidedDocs/15/NCT02360215/Prot_SAP_000.pdf
12. Brown PD, Gondi V, Pugh S, et al. Hippocampal avoidance during whole-brain radiotherapy
plus memantine for patients with brain metastases: phase III trial NRG oncology CC001. J
Clin Oncol. 2020;38(10):1019-1029. https://doi.org/10.1200/JCO.19.02767
13. Ehsani O, Pouladian M, Toosizadeh S, Aledavood, SA. Registration and fusion of 3D surface
data from CT and ToF camera for position verification in radiotherapy. SN Appl Sci.
2019;1(11). https://doi.org/10.1007/s42452-019-1350-2
14. Lawrence YR, Li XA, el Naqa I, et al. Radiation dose-volume effects in the brain. Int J
Radiat Oncol Biol Phys. 2010;76(3 Suppl):S20-S27.
https://doi.org/10.1016/j.ijrobp.2009.02.091
15. Yuen AHL., Wu PM., Li AKL, et al. Volumetric modulated arc therapy (VMAT) for
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and split-arc partial-field techniques. Radiat Oncol. 2020;15(42).
https://doi.org/10.1186/s13014-020-01488-5
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Figures

Figure 1. Patient simulation position for the HS-WBRT planning CT and treatments.

Figure 2. Planning technique “A” field designs showing an example of the field for the
clockwise (CW) and counterclockwise (CCW) full arcs (A) and the sagittal arcs using split-x
technique that separates the brain into left and right sides (B).

Figure 3. Planning technique “B” field designs showing an example of the fields for the CW and
CCW arcs with split-x technique separating the brain into superior and inferior portions (A) and
the sagittal arcs with split-x technique separating the brain into left and right sides (B).
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Figure 4. Planning technique “C” field designs showing an example of the fields for the CW and
CW arcs with the couch at 355° (A), the CW and CCW arcs with the couch at 5° (B), and the
sagittal arc (C).
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Tables
Table 1. Constraint table for the NRG-CC001 protocol.
Name of Structure Dosimetric Parameter Per Protocol [Gy] Variation Acceptable [Gy]
PTV_3000 D2% ≤37.5 37.5-40
D98% >25 22.5-25
V30Gy >95 90-95
Hippocampi D100% ≤9 9-10
Dmax ≤16 16-17
OpticNerve_R Dmax ≤30 30-37.5
OpticNerve_L Dmax ≤30 30-37.5
Optic Chiasm Dmax ≤30 30-37.5
Gy= Gray, PTV=planned treatment volume, D2%=dose to 2%, D98%=dose to 98%, V30Gy=Volume at 30 Gy,
D100%=dose to 100%, R=right, L=left, Dmax=dose maximum

Table 2. Planning technique “A”, “B”, and “C” arc arrangements.

Technique Field ID Gantry Rtn Collimator Couch Rtn
[degrees] Rtn [degrees] [degrees]
“A” CW 181-179 30 0
CCW 179-181 330 0
Sag Arc CW 181-340 90 270
Sag Arc CCW 340-181 90 270
“B” CCW 179-181 95 0
CW 181-179 85 0
Sag Arc CCW 179-25 80 270
Sag Arc CW 25-179 100 275
“C” CCW T355 179-181 330 355
CW T355 181-179 30 355
CCW T5 179-181 330 5
CW T5 181-179 30 5
CCW T90 179-20 330 90
CW=clockwise, CCW=counterclockwise, SAG=sagittal, Rtn=rotation, T355=table at 355° rotation, T5=table at 5°
rotation, T90=table at 90°rotation

Table 3. Dose statistics for Dmax of the hippocampi for each planning technique using the 10
patient data sets. The shaded columns highlight the planning technique with the lowest
hippocampi dose for each patient data set.
Hippocampi Dmax (Gy)
Patient Data Set Technique “A” Technique “B” Technique “C”
Patient 1 15.18 13.09 15.26
Patient 2 15.90 15.28 15.52
Patient 3 14.19 14.81 16.30
Patient 4 15.38 14.58 14.96
Patient 5 16.60 14.39 12.02
Patient 6 14.47 15.10 15.46
Patient 7 15.82 13.72 15.50
Patient 8 15.34 15.44 16.34
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Patient 9 13.86 11.81 14.59

Patient 10 14.24 13.66 15.81
MEAN HC DOSE 15.10 14.19 15.18
HC=Hippocampi, Gy=Gray

Table 4. PTV D2% for each planning technique using the 10 patient data sets. The shaded
columns highlight the planning technique with the lowest PTV D2% for each patient data set.
PTV D2% (Gy)
Patient Data Set Technique “A” Technique “B” Technique “C”
Patient 1 32.65 35.83 32.19
Patient 2 37.09 32.67 35.74
Patient 3 32.17 32.72 35.78
Patient 4 33.18 32.85 32.38
Patient 5 36.59 38.66 37.63
Patient 6 36.31 33.65 33.92
Patient 7 33.75 33.60 33.65
Patient 8 34.18 32.91 34.06
Patient 9 34.37 33.60 33.82
Patient 10 35.83 33.64 37.04
MEAN D2% 34.61 34.01 34.62
D2%=dose to 2%, Gy=Gray

Table 5. The average dose of each NRG-CC001 dose constraint for each planning technique.
Average Dose (Gy)
Structure Technique “A” Technique “B” Technique “C”
Left Optic Nerve 30.48 29.54 30.41
Right Optic Nerve 30.37 29.65 30.05
Optic Chiasm 30.06 29.77 30.79
PTV D2% 34.61 34.01 34.62
Hippocampus D100% 8.91 8.87 8.44
Gy=Gray, D2%=dose to 2%, D100%=dose to 100%

Table 6. The results for each planning technique and patient data set in accordance to the NRG-
CC001 dose constraints for the PTV D2%, Hippocampi D100%, optic chiasm, and optic nerve. If all
constraints were met per protocol (shaded), if one or more constraints variation acceptable.
Patient Technique “A” Technique “B” Technique “C”
Patient 1 Per Protocol Variation Acceptable Variation Acceptable
Patient 2 Variation Acceptable Per Protocol Variation Acceptable
Patient 3 Per Protocol Per Protocol Variation Acceptable
Patient 4 Per Protocol Per Protocol Per Protocol
Patient 5 Variation Acceptable Variation Acceptable Variation Acceptable
Patient 6 Per Protocol Per Protocol Variation Acceptable
Patient 7 Variation Acceptable Variation Acceptable Variation Acceptable
 1

Patient 8 Variation Acceptable Variation Acceptable Variation Acceptable

Patient 9 Variation Acceptable Variation Acceptable Per Protocol
Patient 10 Variation Acceptable Variation Acceptable Variation Acceptable
D2%=dose to 2%, D100%=dose to 100%