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, RT(T); and
Matt Tobler, CMD, RT(T), FAAMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI

Abstract
Whole brain radiation therapy (WBRT) can cause damage to the hippocampi and result in
adverse neurocognitive effects. New planning techniques and protocols for hippocampus-sparing
whole brain radiation therapy (HS-WBRT) have been implemented with advancements in
technologies. The purpose of this retrospective study was to compare 3 volumetric modulated arc
therapy (VMAT) planning techniques to determine if 1 could produce plans that reduced the
maximum dose (Dmax) to the hippocampi to < 16.0 Gy and the dose to 2% (D2%) of the PTV to <
115% or 34.50 Gy. Ten HS-WBRT patients were selected and the 3 planning techniques were
optimized using constraints from the team of researchers formed by the National Surgical
Adjuvant Breast and Bowel Project (NSABP), the RTOG, and the Gynecologic Oncology Group
(GOG) known as NRG Oncology (NRG) and the hippocampus avoidance CC001 phase III trial.
The hippocampi Dmax, PTV D2%, and NRG constraints were compared between the 3 planning
techniques. The dose statistics for the hippocampi Dmax and PTV D2% of each planning technique
on the 10 data sets were evaluated using the Friedman’s test which resulted in P=0.08208 for the
hippocampi Dmax and P=0.04505 for the PTV D2% which were not statistically significant.
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 have been estimated to be around 70,000 to 400,000 newly
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
 2

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 sufficient coverage of the
whole brain but have not been useful 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 seen 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 generated new treatment options for WBRT
including intensity modulated radiation therapy (IMRT) and volumetric modulated radiotherapy
(VMAT). These new treatment options have shown comparable dose coverage of the whole
brain with lower dose to OAR.6 This has enabled hippocampal sparing (HS)-WBRT VMAT
planning. 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 during this study 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 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 formed by the National Surgical Adjuvant Breast and Bowel
Project (NSABP), the RTOG, and the Gynecologic Oncology Group (GOG) known as NRG
Oncology (NRG) initiated the hippocampus avoidance CC001 phase III trial. Researchers
 3

involved in this trial discovered that reducing hippocampal radiation dose along with adding
memantine had similar positive results in reduced cognitive toxicity at follow-up appointments 4
to 6 months after HS-WBRT.1,5 The steep dose-response relationship between radiation dose to
the hippocampi and cognitive decline has suggested that tighter dose constraints may be
beneficial.7 Incorporation of complex IMRT techniques utilized for this protocol not only allows
for dose reduction to the hippocampi, but provides the planner with the added advantage of
reducing dose to the optic structures.
Hippocampus sparing WBRT treatment planning can be labor-intensive. Meeting the
hippocampus dose constraint in the NRG-CC001 protocol can also result in unwanted high doses
to the normal brain and OAR which can result in radiation-induced side effects.10 The problem is
that high dose to the hippocampi can affect neurocognitive function in patients, and increased
dose within the treatment volume causes radiation-induced side effects. The purpose of this study
was to compare 3 unique VMAT HS-WBRT techniques that decrease the dose to the hippocampi
and hot spots within the treatment volume while maintaining PTV coverage and following the
NRG-CC001 dose constraints. Researchers tested the hypotheses that, while maintaining PTV
coverage and meeting the NRG-CC001 dose constraints for the optic structures, 1 of the VMAT
planning techniques will produce a HS-WBRT planning technique that will (H1A) decrease the
maximum dose (Dmax) to the hippocampi to < 16.0 Gy and (H2A) will reduce the maximum dose
to 2% (D2%) within the treatment volume to < 115% (34.50 Gy) of the prescribed dose.
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 BM or PCI. The
prescription dose was 30 Gy in 10 fractions, treated once daily. All patients underwent a CT
simulation in the supine, head-first position using a thermoplastic 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
 4

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 planned
treatment volume (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 the treatment planning was done by one researcher using the Eclipse treatment
planning system (TPS). The algorithm used for dose calculation was the anisotropic analytical
algorithm (AAA) version 16.1.0. All HS-WBRT VMAT plans used the Varian TrueBeam STX
with high-definition MLC’s (HD-MLCs) including 32 central 2.5 mm width and 28 outer 5 mm
width MLC’s. The isocenter for all plans was placed near the center of the brain. Each plan
utilized 6 MV flattening filter-free (FFF) beams.
Three different HS-WBRT planning techniques were compared in this research study.
These techniques have been used by medical dosimetrists at 3 cancer centers. Each plan had a
unique arrangement of beam angles and field designs. 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 and Table 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 and Table 3). VMAT planning technique “C” used 4 full
arcs and a sagittal arc with fields covering the entire brain (Figure 4 and Table 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
hippocampus avoidance region and given an upper and lower objective, with the upper being
slightly higher than the prescription and the lower limit being < 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 hot
spot reduction. The hippocampus was given two upper objectives, D100% < 9.0 Gy and Dmax < 16.0
Gy, and this structure’s objectives were given the second highest priorities. Finally, all the
 5

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 and lower the dose to the hippocampi and hot
spots 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 the treatment volume
D2%. The hippocampi were assessed based on the maximum dose (Dmax), with the goal being <
16.0 Gy, per this research’s hypothesis (H1A), although NRG-CC001 variation acceptable limit is
<17.0 Gy. Furthermore, the D2% was compared between planning techniques with the goal being
< 115%, or 34.50 Gy for the hypothesis (H2A), although NRG-CC001 protocol variation
acceptable limit is <40.0 Gy.
Statistical Analysis
The data from each planning technique was compared for each of the evaluated metrics
including the hippocampi Dmax and D2% of the treatment volume. Due to the multiple variables
and non-parametric data, the Friedman’s test was performed to compare the difference in these
statistics between the 3 VMAT HS-WBRT planning techniques. The significance value was P <
0.1, if P < 0.1 then the research fails to reject the null hypothesis.
Results
Hippocampi Dose
The hippocampi Dmax dose between the 3 HS-WBRT planning techniques ranged from a
minimum of 12.02 Gy to a maximum of 16.60 Gy (Table 5). There were a total of 3 plans that
were unable to meet the objective of the Dmax to the hippocampi < 16.0 Gy for the hypothesis
(H1A), however they achieved the variation acceptable protocol limit of <17.0 Gy. The average
hippocampi Dmax dose for planning technique “A” was 15.10 Gy, planning technique “B” was
14.19 Gy, and planning technique “C” was 15.18 Gy. Planning technique “B” resulted in 6 out of
the 10 patient data sets with the lowest hippocampi Dmax between the 3 planning techniques.
Additionally, the average D100% of the hippocampi was 8.91 Gy for technique “A”, 8.87 Gy for
technique “B”, and 8.44 Gy for technique “C”. The data from the hippocampi Dmax on each
 6

patient for each planning technique was input into the Friedman’s test and resulted in a
P=0.08208. Therefore, the null hypothesis H10 failed to be rejected.
D2% of the Treatment Volume
The D2% to the treatment volume was evaluated between the 3 HS-WBRT planning
techniques and ranged from 107.2% (32.17 Gy) to 128.9% (38.66 Gy) (Table 6). The average
D2% for planning technique “A” was 115.37% (34.61 Gy), planning technique “B” was 113.4%
(34.01 Gy), and planning technique “C” was 115.4% (34.62 Gy). Planning technique “B”
resulted in 7 out of the 10 patient data sets with the lowest D2%. The data from each planning
technique’s maximum dose on each patient data set was input into the Friedman’s test which
resulted in P=0.04505. Therefore, the null hypothesis H20 failed to be rejected.
NRG-CC001 constraints
The average dose for each NRG-CC001 constraint metric was calculated (Table 7). The
average dose measurements from Table 7 showed that the OAR dose constraints were on average
very close to the protocol requests. Although, of the 30 total plans created only 10 plans met all
the constraints of the NRG-CC001 protocol at the protocol request, all the other plans had at
least 1 constraint that met the variation acceptable constraint (Table 8).
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 al. study assessed the effects of HS-WBRT and have demonstrated that
VMAT planning could reduce hippocampal dose and the associated neurocognitive toxicity.12
The established relationship between bilateral hippocampi maximum dose and short-term
memory deterioration, even with patients who have met protocol hippocampal constraints,
suggested tighter constraints could be beneficial.7 In NRG-CC001, Dmax of 14 Gy and 16 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 average hippocampi Dmax for
the 3 planning techniques was not much lower than 16 Gy. Although it would be beneficial to
decrease the Dmax of the hippocampi further, it is difficult to reduce the dose to the hippocampi
without compromising dosimetric plan quality because of its central location.
 7

Additionally, radiation toxicities can occur from increased radiation dose to the brain or
OAR from dose heterogeneities or hot spots. The incidence and severity of the toxicities are dose
and volume dependent.14 This is why it is important to attempt to decrease hot spots and
unnecessary dose to OAR. The NRG-CC001 protocol established set constraints for the
maximum dose to OAR and the treatment volume. However, in the NRG protocol the PTV D2%
is acceptable to be up to 133% (40.0 Gy) and the Dmax for the optic structures up to 125% (37.50
Gy). Since vision deterioration has been an issue with WBRT and increased dose to the brain can
cause functional decline, the present 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 In this study the
D2% < 34.5 Gy was only achievable in 20 of the 30 patient plans. Although, the average for the
data of the D2% was around 115% and for the Dmax of the optic structures was around 30.0 Gy for
all 3 HS-WBRT plans. This suggests that the protocol constraints are achievable but not
necessarily able to be significantly surpassed with the planning techniques used.
Overall, planning technique “B” seemed to be the most promising for both metrics tested
in this study. 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% of the PTV < 115%
(34.50 Gy). The promising results of planning technique “B” may be attributed to the 4 arcs all
having partial-fields by using split-x technique. Large irradiation 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 without having to travel as far. This could enable the MLCs to block the hippocampi and
other OAR more efficiently throughout each arc.
Conclusion
The problem is that high dose to the hippocampi can affect neurocognitive function in
patients, and increased dose within the treatment volume causes radiation-induced side effects.
The purpose of this study was to compare 3 unique VMAT HS-WBRT techniques that decrease
the dose to the hippocampi and hot spots within the treatment volume while maintaining PTV
coverage and following the NRG-CC001 dose constraints. The use of the 3 HS-WBRT VMAT
planning techniques to reduce the Dmax dose to the hippocampi (P=0.08208) and the maximum
dose within the treatment volume (P=0.04505) were not statistically significant.
 8

One of the limitations of this study is that all the patients were collected from a single
institution with the same treatment planning system and algorithm. Although this creates
consistency within the treatment planning and reduces variables, the results of this study may
differ with a different TPS, machine, or algorithm. Other limitations include the small population
of HS-WBRT patient data sets used (10) to evaluate the 3 planning techniques. Future research
should use a different TPS, linear accelerator, and treatment algorithm on a larger number of
patient data sets.
 9

References
1. Liu H, Clark R, Magliari A, et al. Rapid plan hippocampal sparing whole brain model
version 2 – how far can we reduce dose? Med Dosim. 2022;47:258-263.
https://doi.org/10.1016/j.meddos.2022.04.003
2. Lamba N., Wen P.Y., Aizer A.A. Epidemiology of brain metastases and leptomeningeal
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
0933 trial. Radiat Oncol. 2017;12:161. https://doi.org/10.1186/s13014-017-0896-7
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
 10

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
hippocampal-avoidance whole brain radiation therapy: planning comparison with dual-arc
and split-arc partial-field techniques. Radiat Oncol. 2020;15(42).
https://doi.org/10.1186/s13014-020-01488-5
 11

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 CW and
CCW full arcs (left) and the sagittal arcs using split-x technique that separates the brain into left
and right sides (right).

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 (left) and
the sagittal arcs with split-x technique separating the brain into left and right sides (right).
 12

Figure 4. Planning technique “C” field designs showing an example of the fields for the CW and
CW arcs with the couch at 355° (left), the CW and CCW arcs with the couch at 5° (middle), and
the sagittal arc (right).
 13

Tables
Table 1. Constraint table for the NRG-CC001 protocol.
Name of Structure Dosimetric Parameter Per Protocol Variation Acceptable
PTV_3000 D2% (Gy) ≤37.5 37.5-40
D98% (Gy) >25 22.5-25
V30Gy (%) >95 90-95
Hippocampi D100%(Gy) ≤9 9-10
Dmax(Gy) ≤16 16-17
OpticNerve_R Dmax(Gy) ≤30 30-37.5
OpticNerve_L Dmax(Gy) ≤30 30-37.5
Optic Chiasm Dmax(Gy) ≤30 30-37.5
PTV=planned treatment volume, D2%=dose to 2%, D98%=dose to 98%, V30Gy=Volume at 30 Gy, D100%=dose to
100%, Dmax=dose maximum

Table 2. Planning technique “A” arc arrangements showing 2 full arcs with the couch at 0° and 2
sagittal arcs with the couch at 270°
Field ID Gantry Rtn Collimator Couch Rtn
[deg] Rtn [deg] [deg]
CW 181-179 30 0
CCW 179-181 330 0
Sag Arc CW 181-340 90 270
Sag Arc CCW 340-181 90 270
CW=clockwise, CCW=counterclockwise, SAG=sagittal, Rtn=rotation, deg=degrees

Table 3. Planning technique “B” arc arrangements showing 2 full arcs with the couch at 0° and 2
sagittal arcs with the couch at 270° and 275°.
Field ID Gantry Rtn Collimator Couch Rtn
[deg] Rtn [deg] [deg]
CCW 179-181 95 0
CW 181-179 85 0
Sag Arc CCW 179-25 80 270
Sag Arc CW 25-179 100 275
CW=clockwise, CCW=counterclockwise, SAG=sagittal, Rtn=rotation, deg=degrees

Table 4. Planning technique “C” arc arrangements showing 4 full arcs with the couch at 355°
and 5° and the sagittal arc with the couch at 90°.
Field ID Gantry Rtn Collimator Couch Rtn
[deg] Rtn [deg] [deg]
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, Rtn=rotation, deg=degrees
 14

Table 5. Dose statistics for Dmax of the hippocampi for each planning technique using the 10
patient data sets.
HIPPOCAMPI (Gy) 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
Patient 9 13.86 11.81 14.59
Patient 10 14.24 13.66 15.81
AVERAGE HC DOSE 15.10 14.19 15.18
HC=Hippocampi

Table 6. PTV D2% for each planning technique using the 10 patient data sets.
PTV D2% (Gy) 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
Average D2% 34.61 34.01 34.62
D2%=dose to 2%

Table 7. The average dose of each NRG-CC001 dose constraint for each planning technique.
Average Dose (Gy) 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

Table 8. 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 (gray), if one or more constraints variation acceptable.
GOALS Technique “A” Technique “B” Technique “C”
 15

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
Patient 8 Variation Acceptable Variation Acceptable Variation Acceptable
Patient 9 Variation Acceptable Variation Acceptable Per Protocol
Patient 10 Variation Acceptable Variation Acceptable Variation Acceptable