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A case study of precentral gyrus dose when controlling 36 metastatic brain lesions with
SRT, WBRT-HA and WBRT

Authors: Jeremy Marshall, R.T.(T), Evangelia Andrews, Erika Winn, Nishele

Lenards, Ph.D., CMD, R.T.(R)(T), FAAMD, Ashley Hunzeker, M.S., CMD, Matt Tobler, CMD,
R.T.(T), FAAMD

Medical Dosimetry Program at the University of Wisconsin – La Crosse

Abstract
Introduction
The hippocampus is a sensitive neural structure located deep in the temporal lobe which
plays an instrumental role in learning and memory. While the hippocampi are present in all
vertebrates, the human brain is set apart by its relatively large frontal lobe, which allows for
high-level cognitive abilities such as consciousness, communication, and advanced problem
solving.1 There are various neural structures that make up the frontal lobe, each responsible for a
different higher-order task. One of these structures is the precentral gyrus. Often referred to as
the primary motor cortex, the precentral gyrus is found anterior to the central sulcus, expands
laterally on each frontal lobe, and is responsible for voluntary motor control.2 Despite the
importance of the precentral gyrus, it is very rarely considered a dose limiting structure in
radiation treatment planning.
A fundamental pillar of radiation oncology is to keep dose to healthy tissue as low as
reasonably achievable (ALARA). For cranial irradiation, whole brain radiotherapy (WBRT) is
often employed for prophylactic treatments and control of metastatic disease, as it has been
shown to effectively control metastases while reducing chance of death due to neurologic
causes.3 Unfortunately, with the nature of WBRT, an excessive amount of healthy tissue is
exposed to radiation, leading to cognitive deficits. Whole brain radiotherapy has been associated
with declines in memory, attention, and processing in up to 75% of patients during treatment.2
Specific to radiation therapy, researchers have suggested that low levels of radiation exposure to
the hippocampus may contribute to radiotherapy-induced cognitive toxicity, and subsequently,
treatment techniques have been adapted to avoid this structure.1 Stereotactic radiotherapy (SRT)
and whole brain radiotherapy- hippocampal avoidance (WBRT-HA) are 2 methods adapted for
cranial irradiation.
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To keep dose to healthy tissue minimized, SRT and WBRT-HA techniques are often
utilized clinically for primary and metastatic brain lesions. Compared to WBRT, SRT is
associated with a reduced risk of neurocognitive side effects in patients with 1- 3 brain
metastases.3 With WBRT-HA techniques, the hippocampi are avoided while prescription dose is
delivered to the rest of the brain, resulting in a lesser risk of cognitive failure compared to
WBRT.1 The effectiveness of SRT and WBRT-HA stems from the ability to avoid and preserve
cognitive tissue, however, the researchers of this case study question if there is an upper limit on
the number of metastatic lesions treated before the cognitive tissue preservation becomes
equivalent to WBRT.
The brain, unlike most organs, is an elaborate system with fundamentally and
functionally different areas. Current Quantitative Analysis of Normal Tissue Effects in the Clinic
(QUANTEC) data for the brain is limited, indicating dose constraints for the whole brain,
brainstem, and hippocampus, even though there are many critical areas and neural structures
within the brain that are unaccounted for. The problem is that the precentral gyrus is rarely
considered a dose limiting treatment planning structure despite known motor and cognitive
deficits associated with irradiation. The researchers seek to evaluate the precentral gyrus dose in
an extreme case where 36 metastatic brain lesions were treated with SRT compared to traditional
WBRT or WBRT-HA. The first goal of this case study is to identify the precentral gyrus dose for
SRT, WBRT-HA, and traditional WBRT. The second goal of the case study is to evaluate the
necessity for SRT according to precentral gyrus dose.

Case Description
Patient Demographics and Setup
Treatment with SRT is associated with a reduction in neurocognitive side effects in patients with
1-3 brain lesions compared to patients treated with WBRT.3 The researchers of this case study
aimed to evaluate precentral gyrus sparing for an SRT patient who greatly exceeded 3 metastatic
lesions. Distribution of lesions within the frontal lobe and their proximity to the precentral gyrus
was also considered. Ultimately, an SRT patient with 36 metastatic brain lesions was chosen; 18
of those 36 lesions were housed within the frontal lobe with varying distance to the precentral
gyrus.
For simulation, the patient was positioned headfirst supine with arms down and at their
sides and knees elevated slightly with a cushion for comfort. Immobilization utilized for
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simulation included a CDR board with custom mask and cranial mold. A Philips Brilliance big
bore computed tomography (CT) scanner was used to scan the patient with a slice thickness of
1.0 mm. Three radiopaque localization markers were placed on the patient’s mask, 2 laterally
and 1 anteriorly. These radiopaque markers would be utilized for treatment planning and
treatment setup.
Structure Delineation
The CT images obtained in simulation were fused with an MRI scan of the patient’s
brain, which aided in structure delineation. Eclipse version 16.1 was utilized for structure
contouring. Organs at risk (OAR) were contoured by the medical dosimetrist and consisted of the
brainstem, eyes, optic chiasm, and optic nerves. Additional contours were created by the
physician and included the hippocampi, precentral gyrus, and gross tumor volumes (GTVs) for
each of the 36 metastatic lesions. A 0.2 cm expansion was added to the GTVs which established
the planning treatment volumes (PTVs).
The precentral gyrus is found on the lateral surface of the brain. It runs parallel to the
central sulcus on the frontal lobe, ends at the anterior sulcus, and extends inferiorly to the
lateral sulcus.2 Of the 36 total metastases treated, 18 were of particular interest as they
were located superior to the lateral sulcus (Figure 1). The total volume and distance from the
precentral gyrus for each of the 18 PTVs of interest were recorded (Table 1). Two of the 18
targets overlapped with the precentral gyrus and 2 additional metastases were less than 1.0 cm
away.
Treatment Planning
Treatment planning was also performed using Eclipse version 16.1. The treatment
planning constraints used for planning were based on department standards as well as constraints
outlined by Brown et al (Table 2).3 All OAR constraints were met for their respective treatment
modality, and any constraint not specified by department standards was below QUANTEC
limits.
The 2 isocenter SRT plan was designed in a way which divided the brain into anterior
and posterior halves; one isocenter was placed in the anterior portion and the other was placed in
the posterior portion. The treatment plan consisted of 18 stereotactic radiosurgery (SRS) rapid
arc beams which used various couch angles and collimator rotations to ensure OAR sparing and
acceptable PTV coverage (Table 3). The energy utilized for this plan was 6 MV flattening filter-
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free (FFF) photons and an overall plan normalization of 98% was set. Treatments occurred once
every other day and the prescription dose, delivered by a Varian TrueBeam linear accelerator,
was 27 Gy in 3 fractions.
Two plans were generated retrospectively for comparison of precentral gyrus dose
against that which was received by SRT. For the most accurate comparison across treatment
techniques, the plans were created using 6 MV photons to be delivered on a Varian TrueBeam
linear accelerator. For the WBRT, beam arrangement consisted of the traditional parallel
opposed static fields at 90° and 270°. A single isocenter was placed in the center of the brain
with equal field weighting, distributing uniform coverage across the brain. The physician utilized
a multileaf collimator (MLC) to ensure adequate blocking around optic structures, oral cavity,
and base of skull. The flash margin around the anterior, posterior, and superior portion of the
skull was set to 2.0 cm. The dose was normalized to the midplane of the brain. Treatments
occurred once daily, 5 days a week with the prescription dose being 30 Gy in 10 fractions.
The second plan was a WBRT-HA plan which consisted of 6 coplanar static beams,
spaced out for adequate coverage. The isocenter was placed in the center of the brain and the
PTV was defined as the whole brain excluding the hippocampi. Each treatment field utilized
MLC blocks fit to the PTV with a 0.5 cm margin. Critical structures were blocked to ensure
OAR constraints would be met. The gantry angles used were 355°, 50°, 110°, 185°, 225°, and
300°. There were no couch rotations or collimator rotations for this treatment technique. The
plan was normalized for 98% of the prescription dose to cover 98% of the PTV. Treatments
occurred once daily, 5 days a week, with the prescription dose being 25 Gy in 10 fractions.
Plan Analysis and Evaluation
Given the differences in dose and fractionation for the different techniques, both relative and
absolute maximum, mean, and minimum dose to the precentral gyrus were recorded (Table 4).
Stereotactic radiotherapy yielded the lowest relative minimum, maximum, and mean dose to the
precentral gyrus at 19.4%, 102.7%, and 31.6% respectively. The lowest mean dose to the
precentral gyrus was a result of SRT at 853 cGy. By comparison, WBRT-HA had the lowest
absolute maximum dose to the precentral gyrus of 2477 cGy and the highest relative maximum
dose to the precentral gyrus of 109.8% prescription.
When creating the retrospective studies, the researchers aimed to create a plan which
would meet dose constraints and could be treated clinically; the precentral gyrus was not
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intentionally spared in any of the treatment methods. The lowest average dose to the 18 PTVs
came from SRT (2606 cGy, SD = 70 cGy) which also had the lowest relative target dose of
96.5%. The most homogenous PTV coverage came from WBRT (average 3907 cGy SD = 45
cGy). The hottest treatment plan was WBRT-HA with a mean relative dose of 106.0% (2649
cGy SD = 56 cGy).

Conclusion
a. PI: Summarize the purpose of the study
b. PII: Summarize results
c. PIII: Limitations and options for future research
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References

1. Teffer K, Semendeferi K. Human prefrontal cortex. Evolution of the Primate Brain.

2012:191-218. https://doi.org/10.1016/b978-0-444-53860-4.00009-x
2. 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. Clin Onc. 2020;38(10):1019-1029.
https://doi.org/10.1200/jco.19.02767
3. Hardy SJ, Krull KR, Wefel JS, Janelsins M. Cognitive changes in cancer survivors.
ASCO Educational Book. 2018;(38):795-806. https://doi.org/10.1200/edbk_201179
4. Pinkham MB, Whitfield GA, Brada M. New developments in intracranial stereotactic
radiotherapy for metastases. Clin Oncol (R Coll Radiol). 2015;27(5):316-323.
http://doi:10.1016/j.clon.2015.01.007
5.
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Figures

Figure 1. 3D model of the patient shows the precentral gyrus (peach, Left) and the target
volumes (Right).
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Tables

Table 1. Metastatic Lesion Volume, Proximity to Precentral Gyrus, and Any Overlap with
Precentral Gyrus.
Metastatic Distance From Volume of Percentage Overlap with Precentral
Lesion Precentral Lesion (cc) Gyrus
Gyrus (cm)
1 3 0.07 0
2 0.62 0.04 0
3 1.5 0.08 0
4 3.38 0.03 0
5 2.41 0.05 0
6 0 0.03 0.33
7 3.81 0.02 0
8 0.76 0.33 0
9 3.28 0.21 0
10 5.37 0.16 0
11 2.78 0.03 0
12 1.78 0.13 0
13 4.96 0.08 0
14 3.84 0.03 0
15 5.72 0.06 0
16 7.19 0.01 0
17 4.23 0.05 0
18 0 0.06 0.5

Table 2. Dose Constraints for the Organs at Risk Utilized During Treatment Planning.
Structure SRT (Gy) WBRT (Gy) WBRT-HA (Gy)

Dmax = 15.0
Brainstem N/A Same as WBRT
V10 < 0.5 cc

Eyes Dmax = 2.0 Dmax < 33 Same as WBRT

Dmax < 33
Optic Chiasm Dmax < 15.3 Dmax ≤ 25

Dmax < 33
Optic Nerves Dmax < 15.3 Dmax ≤ 25

D100% ≤ 7.5
Bilateral Hippocampi N/A N/A
Dmax ≤ 13.5
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*Gray (Gy)

Table 3. Arc Beams, Couch Rotations, and Collimator Angles Used for Planning Stereotactic
Treatment.
Arc Gantry Angles Collimator Couch
Number Angles Rotation
1 25 CW 178 160° 0°
2 178 CCW 30 0° 0°
3 30 CW 178 90° 0°
4 315 CCW 182 135° 0°
5 182 CW 178 160° 0°
6 178 CCW 182 0° 0°
7 40 CW 178 160° 45°
8 178 CCW 40 160° 45°
9 40 CW 178 160° 0°
10 320 CCW 182 135° 0°
11 40 CW 178 15° 0°
12 178 CCW 40 15° 0°
13 182 CW 310 90° 0°
14 310 CCW 182 135° 0°
15 178 CCW 60 135° 0°
16 182 CW 320 135° 0°
17 315 CCW 182 0° 315°
18 182 CW 330 15° 0°

*Clockwise (CW); counterclockwise (CCW)

Table 4. Dose to the Precentral Gyrus Observed for Each Treatment Method
Max Dose Minimum Dose Mean Dose (cGy)
Planning cGy Percent cGy Percent cGy Percent
Technique Prescription Prescription Prescription
Dose Dose Dose
SRT 2773 102.7% 523 19.4% 853 31.6%
WBRT 3209 106.9% 3032 101.0% 3082 102.7%
WBRT-HA 2744 109.8% 2551 102.0% 2663 106.5%
*Centigray (cGy)