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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

I. Abstract
II. Introduction
A. PI: The significance of brain metastases and WBRT treatments (Reference: Liu et al, 1
Lamba,2 Krayenbuehl et al3)
B. PII: Hippocampus anatomy and radiation response (Reference: Liu et al,1 Sprowls et
al,4 Kazda et al5)
C. PIII: Technology advancements and protocols with HS-WBRT constraints
(Reference: Liu et al1, Krayenbuehl et al,3 Sprowls et al,4 Shang et al,6 Sood et al7)
D. PIV: Summarize introduction points and discuss each planning technique (Reference:
Krayenbuehl et al,3 Pokhrel et al,8 Redmond et al9)
E. PV: State the problem and purpose of this study and summarize previous research
1. Problem: 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.
2. Purpose: The purpose of this study is to compare VMAT HS-WBRT techniques
(A, B, C) that decrease the dose to the hippocampi and hot spots in brain tissue
while maintaining PTV coverage and NRG-CC001 OAR dose constraints.
3. Hypotheses: This research will test the hypothesis that one of the three VMAT
HS-WBRT planning techniques will decrease the dose to the hippocampus to <
1600 cGy, while maintaining PTV coverage and NRG-CC001 dose constraints
(H1A). It will also test the hypothesis that one of the three VMAT planning
techniques will reduce hot spots within the brain tissue to < 115% of the
prescribed dose, while maintaining PTV coverage and NRG-CC001 dose
constraints (H2A).
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III. Material and Methods

A. Patient selection and setup
1. PI: Patient Population
a. 10 Patients
b. Inclusion criteria (Hippocampus sparing whole brain treatments planned with
VMAT; 30 Gy in 10 fx, once daily)
c. Exclusion criteria (3DCRT or IMRT techniques)
d. Patient simulation set-up (Figure 1)
B. Contours (Reference: NRG10)
1. PI: NRG-CC001 protocol contours (Table 1)
a. PTV (the whole brain)
b. Hippocampi and margins
c. OAR (optic structures)
C. Treatment Planning
1. PI: Planning details
a. Treatment planning system (Eclipse)
b. Machine (Varian TrueBeam STX with HD-MLCs)
c. Algorithm (AAA 16.1.0)
d. Energies (6MV-FFF)
2. PII-PIV: Planning procedures
a. PII: Field designs, gantry angles (Figures 2, 3, 4)
b. PIII: Table kicks, arc directions (Table 2, 3, 4)
c. PIV: Optimization
D. Plan Comparison
1. PI: Evaluated metrics (Reference: Brown et al11)
a. Hippocampus (D100%, DMax)
b. Target dose (V30, D98%, D2%)
c. OAR dose (DMax)
E. Statistical Analysis
1. PI: Representation of data
a. Data for the dose to the hippocampus (Table 5)
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b. Data for dose to the brain and the maximum dose (Table 6)
c. Data for the dose to OAR (Table 7)
d. Friedman’s test
e. P < 0.1 considered statistically significant
IV. Results
A. PI: Hippocampi (HC) dose
1. D100% HC dose > 900 cGy
2. Dmax HC dose < 1600 cGy (Table 5).
3. Dmax HC dose P < 0.1, research fails to reject the null hypothesis.
B. PII-III: Dose to the brain (V30Gy, D98%, D2%)
1. Target dose V30Gy > 90-95%
2. Target dose D98% > 22.5-25 Gy
3. Target dose D2% < 115% or 3450 cGy (Table 6)
4. D2% P < 0.1, research fails to reject the null hypothesis.
C. PIV: OAR Dmax Dose
1. Optic chiasm Dmax dose < 30-37.5 Gy
2. Right optic nerve Dmax dose < 30-37.5 Gy
3. Left optic nerve Dmax dose < 30-37.5 Gy
4. Average results for OAR Dmax (Table 7)
D. PV: Constraints met per protocol or variation acceptable (Table 8)
V. Discussion
A. PI: Summarize hippocampi dose results in comparison to each planning technique
B. PII: Summarize brain dose results in comparison to each planning technique
C. PIII: Summarize OAR max dose results in comparison to each planning technique
D. PIV: Summarize all results in study to recap and which planning technique did best
with each dose constraint.
VI. Conclusion
A. PI: Summarize the study
1. Problem: 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.
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2. Purpose: The purpose of this study is to compare VMAT HS-WBRT techniques

(A, B, C) that decrease the dose to the hippocampi and hot spots in brain tissue
while maintaining PTV coverage and NRG-CC001 OAR dose constraints.
B. PII: Limitations/future research
1. Limitations: all patients were collected from one institution with the same
treatment planning system and algorithm.
2. Future Research: a larger group of patients from several institutions across the
nation with more than three planning techniques.
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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
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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. 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.
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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 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).
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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° (left), the CW and CCW arcs with the couch at 5° (middle), and
the sagittal arc (right).
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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

Table 2 . Planning technique “A” arc arrangements showing 2 full arcs with the couch at 0° and

2 sagittal arcs with couch at 270°.

Field ID Energy MLC Gantry Rtn Colli Rtn Couch Rtn

[deg] [deg] [deg]
CW 6X-FFF VMAT 181-179 30 0
CCW 6X-FFF VMAT 179-181 330 0
Sag Arc CW 6X-FFF VMAT 181-340 90 270
Sag Arc CCW 6X-FFF VMAT 340-181 90 270
CW=clockwise, CCW=counterclockwise, SAG=sagittal, FFF=Flattening Filter Free

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 Energy MLC Gantry Rtn Colli Rtn Couch Rtn
[deg] [deg] [deg]
CCW 6X-FFF VMAT 179-181 95 0
CW 6X-FFF VMAT 181-179 85 0
Sag Arc CCW 6X-FFF VMAT 179-25 80 270
Sag Arc CW 6X-FFF VMAT 25-179 100 275
CW=clockwise, CCW=counterclockwise, SAG=sagittal, FFF=Flattening Filter Free

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 Energy MLC Gantry Rtn Colli Rtn Couch Rtn
[deg] [deg] [deg]
CCW T355 6X-FFF VMAT 179-181 330 355
CW T355 6X-FFF VMAT 181-179 30 355
CCW T5 6X-FFF VMAT 179-181 330 5
CW T5 6X-FFF VMAT 181-179 30 5
CCW T90 6X-FFF VMAT 179-20 330 90
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CW=clockwise, CCW=counterclockwise, FFF=Flattening Filter Free

Table 5. Dose statistics for Dmax of the hippocampus for each planning technique using the 10
patient data sets.
HIPPOCAMPUS Technique “A” Technique “B” Technique “C”
Patient 1 1517.86 1309.27 1525.93
Patient 2 1590.27 1527.95 1551.89
Patient 3 1418.65 1480.76 1629.65
Patient 4 1537.84 1457.62 1495.58
Patient 5 1660.35 1439.11 1201.79
Patient 6 1446.74 1510.18 1546.41
Patient 7 1581.99 1371.49 1549.82
Patient 8 1533.86 1544.43 1634.33
Patient 9 1385.87 1180.61 1459.03
Patient 10 1424.47 1366.35 1580.70
AVERAGE HC DOSE 1509.79 1418.78 1517.51
HC=Hippocampus

Table 6. Dose statistics for the maximum dose to the treatment volume for each planning
technique using the 10 patient data sets.
HOTSPOTS Technique “A” Technique “B” Technique “C”
Patient 1 115.4 127.2 112.9
Patient 2 129.2 113.3 125.8
Patient 3 117.2 115.9 124.8
Patient 4 117.7 115.6 118.7
Patient 5 129.3 138.7 134.9
Patient 6 129.9 116.9 116.5
Patient 7 118.1 117.9 118.0
Patient 8 122.7 116.3 120.0
Patient 9 123.9 117.8 118.2
Patient 10 130.1 119.4 129.5
AVERAGE HOTSPOT 123.35 119.9 121.93

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
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Table 8. The results for each planning technique and patient data set in accordance to the NRG-
CC001 dose constraints for the PTV D2%, Hippocampus D100%, optic chiasm, and optic nerve.
If all constraints were met per protocol (gray).
GOALS 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
Patient 8 Variation Acceptable Variation Acceptable Variation Acceptable
Patient 9 Variation Acceptable Variation Acceptable Per Protocol
Patient 10 Variation Acceptable Variation Acceptable Variation Acceptable