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Submission Packet
You are required to submit this packet with each submission of your paper. You
will build on each draft and will also build on each submission packet so it will
represent the changes of your paper from start to finish. In this packet, you will
find:
I. Statements
II. Change Matrix
III. AMA Formatting Checklists
The instructions for each section are listed below. Copy and paste the statement
page, change matrix table and AMA formatting checklist table to the first page
of your draft submission. Remember that you should build on each submission.
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Statements
Remember the problem, purpose and hypotheses statements that we worked so
hard on last semester? We will be using them again! They should be stated in
your paper (just as we worked on in your research proposal) but we are also
asking you to spell them out here as a reminder of the foundational basis for your
research.
Purpose Statement: The purpose of this study is to compare treatment planning techniques and
examine the precentral gyrus dose in an extreme SRT case of 36 metastatic brain lesions.
Problem Statement: 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.
Case Study Goals:
Goal 1: To compare the dose to precentral gyrus between SRT, WBRT-HA, and traditional
WBRT.
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Change Matrix
A change matrix is required with every milestone document submission.

A detailed change matrix simplifies the review process and indicates to the instructors and advisors that
the author has demonstrated a clear and thorough response to reviewer comments.

Reviewer comments are not intended as an exhaustive list. It is the Learner’s responsibility to correct
any additional errors that are not specifically noted by the reviewer and to address the requirements of
the capstone project. All instances where changes have been made should be clearly noted.

If, after discussion with the group, there are questions about a reviewer’s comments, it is the
responsibility of the group leader to reach out to the instructors and advisor via email for clarification.

If, after discussion with the instructors, the author chooses not to make a requested change, the
author must provide a brief rationale, and describe how they addressed reviewer concerns.

Failures to consider, address, and notate within the Change Matrix will result in the manuscript being
returned to the group without comment.

Copy and paste the instructor’s comment from your draft into the matrix.

You will continuously build on this change matrix so that any/all comments can be reviewed at any given
time in the projects progress.

Title of Capstone: A case study of precentral gyrus dose when controlling 36 metastatic brain
lesions with SRT, WBRT-HA and WBRT
Group: Jeremy Marshall, Erika Winn, Evangelia Andrews

Reviewer’s recommendation How addressed Page numbers

where change
appears
Nishele- Studies can't suggest. Researchers Replaced “studies” with” researchers P1
have suggested... Intro. paragraph 2

Matt - Do we need a reference for this
statement?
Nishele- I agree with Matt on the last revision
here that it seems you need a reference citation
here. I am certain you did not come up with
this and the next sentence on your own and
you are not anatomy experts.
Matt - Is this a complete sentence? It doesn't
read like it to me.
Reference for frontal lobe function added. P1
Teffer K, Semendeferi K. Human prefrontal Intro. paragraph 1
cortex. Evolution of the Primate Brain. 2012:191-
218. https://doi.org/10.1016/b978-0-444-53860-
4.00009-x
Reference for anatomic description of precentral
gyrus added.
Ribas GC. The cerebral sulci and gyri.
Neurosurgical Focus FOC. 2010;28(2):E2-.
https://doi.org/10.3171/2009.11.FOCUS09245
Sentence changed, “There are various...” was P1
inserted at the beginning of the sentence. Intro. paragraph 1

Should this read something more like, "There

 4

are various neural structures which make us

the frontal lobe, each respo......."
Matt - I agree with this sentence but it feels Sentence was moved into following paragraph to P1
out of place here as I'm reading the following improve the flow of the piece. Intro. paragraph
paragraph. 1-2
Ashley - Can’t begin sentence with WBRT has been spelled out “Whole brain P1
abbreviation. radiotherapy” Intro. paragraph 2

Nishele - This sentence still does not read Sentence has been broken up into 2 sentences and P1
well. rewritten Intro. Paragraph 2

Ashley - Remove extra space below paragraph Extra space between paragraphs removed P1-2
Intro. paragraph
2-3
Ashley – Spell out first use. Replaced with “Quantitative Analysis of Normal P2
(QUANTEC) Tissue Effects in the Clinic (QUANTEC)” Intro. Paragraph 4

Ashley - Where is the mention of your The previous sentence was replaced with the P2
problem statement? This is the fundamental approved problem statement from RPD. Intro. Paragraph 4
reason why you are doing this research.
Ashley - This is out of order. You should Sentence re-ordered; problem statement first P2
mention your problem statement and your followed by purpose statement. Intro. Paragraph 4
purpose statement first.
Matt - Is this truly SRS (single fraction). From Prescription and fractionation confirmed SRT. All P2
what I've seen, as the number of lesions instances of “SRS” have been replaced with Intro. Paragraph 4
increases the number of fractions needed also “SRT”. References for SRS have been replaced
increases due to the volume of normal brain with references for SRT. (SRS to SRT
being treated. As such, this is no longer revision occurs
considered SRS (single fraction) treatment, across the draft,
but SRT (multi-fraction) brain treatment. from title to
Please clarify. conclusion.)
Ashley - This is not the approved purpose The previous sentence was replaced with the P2
statement from your RPD. approved purpose statement. Ensured sentence Intro. Paragraph 4
order per Ashley’s previous comment.
Ashley - You have no hypothesis, only goals Sentences involving a hypothesis have been P2
of the case study. Go back to the RPD and replaced with approved goals from RPD. Intro. Paragraph 4
review and then incorporate your goals into
the RPD.
Ashley - Remove . after each word Reference has been removed and replaced due to P4
SRS to SRT change. References

Nishele - Is the next sentence after this part of Sentence in question was should have been apart P2
citation #1? If so I would combine the two of citation #1. Sentences were combined as Intro. Paragraph 3
sentences and cite it. Otherwise, I find it hard suggested.
to believe you are the person who know there
is lesser risk of cognitive failure (no citation).
Matt – Please reword. I’m not exactly sure Sentence has been reworded and incorporates P2.
what you’re trying to say here. SRT instead of SRS. Patient Demo.
paragraph 1.
Matt - These sections jump around a bit. First Section has been reorganized per Matt’s P3.
you're talking about mets, then OAR recommendation. Section restructured as follows: Structure
 5

structures, then 2 of the mets, then describing Define OAR, define precentral gyrus location, Delineation
the location of the precentral gyrus, then number of mets, location and proximity to gyrus
talking about the location of mets to the
sulcus. I'd reorganize this some. Talk about
defining organs at risk...then about defining
the precentral gyrus...then about the number of
mets total and the number located in close
proximity of the gyrus.
Matt - As a reader trying to reproduce your Section has been expanded to include more P3-4
technique, can I do it with the information specifics of the treatment planning. Arc angles, Treatment
provided here. If the answer is no, which I collimator rotation, couch rotation, blocking, planning
believe it is, then it needs to be explained energy used, and additional details were included. paragraph 1-4
better. How many transverse arcs were there?
Three of the beams apparently had two
different couch angles, 45 and315 degrees,
which I didn't know you could do with one
rapid arc beam, let alone 3.
Nishele - Technically you shouldn't be posing Sentence has been re-phrased as suggested to P1
a question here. You should re-phrase such avoid posing a question. Intro. Paragraph 3
as ...cognitive tissue; however researchers (or
clinicians) question whether there is an upper
limit...'
Nishele - use scholarly language. Sentence has been removed and replaced to P1.
just say is not contoured ... improve clarity and readability. Intro. Paragraph 4

Nishele - Case study is not evaluating. The Replaced “case study” with “The researchers seek P1
researchers are evaluating... to evaluate...” Intro. Paragraph 4

Nishele - Again - you are giving credit to a Replaced “This retrospective case study aims to P2
non-human thing. Researchers aim to …" with “The researchers aim to evaluate...” Patient Demo.
evaluate... Paragraph 1
also use the greater than symbol

Nishele - And? So what if they were of Section reworded and expanded to provide a P2
interest. better description of the targets which were Structure
I don't feel like you are actually listing out the delineated including GTV identification and Delineation
structures that were delineated. This section is expansion to for PTV. paragraph 1-3
to be specific in which structures were
delineated.

Nishele - This isn't planning section. This is Paragraph moved from structure delineation to P3
contouring. treatment planning section Structure
delineation ->
treatment
planning
Nishele - use degree symbol throughout the “Degrees” was taken out and replaced with P3
paper degree symbol Tx planning
paragraph 2 & 4
Nishele - in 10 what? Section has been rewritten to include more P3-4
You need to write in scholarly language; not specifics of the treatment planning and include Tx planning
slang. And write in completed sentences. scholarly language. paragraph 1-4
 6

Nishele - too short to be a stand-alone Section has been expanded to include more P3-4
paragraph. i assume you'll be expanding this specifics of the treatment planning. Tx planning
section. paragraph 1-4
Matt- This introduction section has an Section has been re-ordered per Matt’s P1
awkward flow for me. I went through it with recommendation. Introduction
numbering in a way that made a little more Paragraph 1-5
sense to me and has what felt like a somewhat
better flow to me. I'd be interested in others
thoughts, but something similar to how I laid it
out might work a little better. All the
information is here, I just think it could be
organized just a bit better to make the intro a
little stronger. It was getting a little mentally
choppy for me toward the end so just give it a
look and see what you think.
Ashley - In the entire intro, it seems to me that Re-ordering of introduction per Matt’s Introduction
you place equal if not more emphasis on the recommendation introduces hippocampi while section –
hippocampi as if it is a goal of your paper. placing more emphasis on the precentral gyrus references
towards the end of the paragraph. reordered
accordingly
Ashley- This should all be simplified. Talk Paragraph has been simplified and changed to P2
about inclusion/exclusion criteria. discuss inclusion/exclusion critera. Paragraph has Patient
This entire paragraph should just talk about been changed to place more emphasis on the demographic
the patient chosen for the case study. patient chosen for case study. Paragraph 1

Ashley - This is introductory material and Sentence was moved to the introduction Introductory
should not be in the material/methods section. paragraph 4

Matt - "followed QUANTEC guidelines." Reworded phrasing from “was below QUANTEC P3 Tx planning
When you say "was below QUANTEC limits" guidelines” to “followed QUANTEC guidelines” paragraph 1
it sounds like you've already done the plan and
evaluated the results.
Matt - Two additional plans, correct? There Sentence has been clarified to indicate that there P4 Tx planning
are 3 plans total, so you'd have the initial 2 iso were 3 plans total, SRT, WBRT, and WBRT-HA paragraph 3
SRT plan plus 2 additional plans, whole brain
and whole brain hippo avoid.
Matt - Was field in field used to limit hot spots Wrote out that field-in-field was not used under P4 Tx planning
for the whole brain? the WBRT planning description paragraph 3

Ashley - ? You just said above that this plan Sentence has been clarified to indicate that the P4 Tx planning
was created retrospectively but it was retrospective plan was not treated but planned paragraph 3
delivered?? This doesn’t make any sense. with a fractionation schedule as though it would
be treated.
Matt - Were critical structures "blocked", or Rephrased for clarity – each plan was optimized P4 Tx planning
was dose to critical structures optimized to to ensure OAR constraints were met paragraph 4
ensure OAR constraints were met?
Ashley - Again, how was this plan delivered?? Sentence has been clarified to indicate that the P4 Tx planning
retrospective plan was not treated but planned paragraph 4
with a fractionation schedule as though it would
be treated.
 7

Ashley- Not relevant as it’s not a goal of your Sentence has been removed as it does not align P5 Plan analysis
research. with our goal paragraph 1

Matt -This is where the plan comparison falls
apart for me. Of course this has the lowest
maximum dose because it has the lowest
prescription dose overall. Additionally, even
though the SRT plan had the lowest mean
dose, that dose was given in 3 fractions where
the mean dose for the other plans was spread
over 10 fractions, so as far as radiobiologic
effect, what does that even mean. I've reached
out to Ashley for suggestions. I'll be interested
in her response.
Resolved in email thread – to paraphrase Ashley, Tables 2 and 4,
rather than reporting any dose in absolute, it P4 Plan analysis
would be reported in a percentage of prescription paragraph 1
dose.
We converted all OAR constraints to percent
prescription and removed absolute dose from
Table 4 where we reported the precentral gyrus
doses.

Ashley - Not relevant as it’s not a goal of your
research. Think back to what the goals were?
Are there meaningful volumetric comparisons
to the gyrus that exist in any kind of literature?
Ashley - You would actually identify 1 image
as “A” and 1 image as “B” and refer to them
that way in your text.
Ashley - I thought you were studying 36
lesions? I know that you selected 18 because
of their location to the gyrus but you should
note that in a footnote so that the reader is not
confused looking at the table.
Ashley - All of the “equations” in this table
need to be spelled out at first use. You will
have to do this in the footnote of your table.
Removed sentence, we were unable to find any P4 – Plan analysis
literature discussing precentral gyrus volumetric and Evaluation
comparisons or sensitivities. paragraph 1
Image has been changed to include an A and B Figure 1A and 1B
label. The footnotes have been changed and
reference to them in the text has been changed.
Footnote has been added for clarification. P8 Table 1.
Additional sentences have been placed in the
inclusion section to improve clarity.
Wrote out the “equations” in proper formatting as Table 2
a footnote.

Matt - I think the paper is coming together Added a few paragraphs to the “plan analysis and Plan anaylsis and
well. Many of the changes made thus far have evaluation” section. Other suggested changes Evaluation –
really helped. I made some additional addressed below. added P1 & P3
suggestions. In particular I think there is much
that can be added to strengthen the "Plan
Analysis and Evaluation" section
Matt - Again I'd rearrange just a little here. Rearranged the paragraph to go WBRT, WBRT- Introduction P3
Start with whole brain, then whole brain-HA, HA, and SRT.
then SRT in a progression that continues to
decrease the amount of normal brain that is
being treated. The two sentences about SRT
almost sound like they repeat so look at them.

Matt - Are you talking about brain tissue only Added this into the paragraph and expanded on Introduction P4
here? Maybe consider expanding to....."When the points
treating patients that require brain treatment,
Quantec currently lists dose limits for
structures such as optic nerve and chiasm,
eyes, lenses and cochlea. For the brain itself,
however, quantec data is limited, indicating
 8

constraints for whole brain tissue, brainstem,

and hippocampus."
Matt - These two sentences basically say the Removed the first sentence in this comment Introduction P5
same thing. I think I'd delete the one in the
upper paragraph and keep the one in the
lower.
Matt - I might use a word more like "optimal" Changed “acceptable” to “optimal” Treatment
here. planning P2

Matt - ??? Removed and reformatted this – it looks like it Treatment

Nishele - So this section needs alot of work. To
me, you haven't provided results in a
comprehensive manner or discussion about
the clinical significance. The Conclusion is a
small summary of the key points along with
limitations of the study.
may be a software issue, the draft does not look planning P3
like this in our working document
Added two paragraphs focusing on the clinical Plan analysis and
significance of the comparison made, the evaluation P1 &
maximum dose, and distribution. P3

Nischele – Why is this DOI listed after the Removed – see Matt’s “???” comment above Plan analysis and
References header? evaluation

Matt - Using relative dose evaluation works. Is Added sentences specifying that the lesion that Plan analysis and
there anything that can be done or said that overlapped with the precentral gyrus was not evaluation P1-P3
would spruce up this paragraph. SRT gave the spared and all lesions were covered with at least
lowest doses in all 3 categories in spite of the 98% of the dose. Added the maximum dose for
fact that 2 of the lesions overlapped the each plan, as well as addressed the potential
precentral gyrus and additional lesions were in trade-offs for the hippocampus dose.
close proximity. You listed the max dose for
the WBRT-HA plan only. What was the max
dose for the other 2 plans? Also, although the
precentral gyrus was the focus of this paper, is
it worth noting the dose to the hippocampus
for each technique? This could potentially
show that, while SRT did getter avoiding the
precentral gyrus, it did worse in avoiding the
hippocampus so there might be a trade off...or
not. Also, did the WBRT-HA technique
potentially miss any lesions that were in close
proximity to that structure?
Matt - Part of your conclusion or final notes Added an additional paragraph into the Conclusion P2
might also include that, similar to introduction conclusion addressing the potential trade-offf
of WBRT-HA technique in years past, potential
consideration may want to be given to
avoidance of other important structures of the
brain including the precentral gyrus. An
additional technique that was not evaluated in
this paper might have been something that
avoided both the hippocampus and the
precentral gyrus.

Matt - You use past tense in the rest of the Changed present to past tense Conclusion P3
 9

paper..."was, were". It's usually best to keep the

same tense throughout the paper, especially
since you are not currently evaluating, you did
evaluate, so the purpose "was" to compare.
This is also true for the last 2 lines of the intro
paragraph where you make similar statements.
Those should also be changed to "was".
Matt - This should be part of your plan analysis Moved to plan analysis section and fixed Plan analysis and
section....and should end in a "." punctuation evaluation P2

Nishele - why is this doi here (and in a Removed formatting – see Matt’s “???” comment References Title
different font style)?

Nishele - Why is this DOI here ??? Removed – see Matt’s “???” comment Figures Title

Nishele - why are these words all capitalized in Kept formatting, it was correct per Niscele No change
this sentence?

Nishele - Make sure this is single line spacing Formatted to be single spaced Table 2
for this description. It looks like there is extra
spacing between the two lines.
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AMA Referencing Quick Guide Checklist

Correctly using AMA formatting is one of the few aspects in the Capstone project that you have
complete control of whether it is your first outline submission or the final draft. Use this AMA quick
guide checklist to avoid common AMA formatting mistakes and receive the greatest number of points
possible. Not everyone has the ability to be an exceptional scholarly writer and researcher, however,
everyone has the capability of using AMA formatting correctly. Review this guide for EVERY submission
(discussion post, outline, draft) in the research courses and ask yourself the following questions:

Task Submiss Submissio Submissio Submissio Submissio Submissio Submissio

ion n Date: n Date: n Date: n Date: n Date: n Date:
Date: 9/19/22 10/3/22
8/5/22

Manuscript
Written in past ☐ ☐ ☒ ☐ ☐ ☐ ☐
tense?
Written in size 12,
☐ ☐ ☒ ☐ ☐ ☐ ☐
Times New Roman
font
Paragraphs include
☐ ☐ ☒ ☐ ☐ ☐ ☐
at least 3
sentences
Page numbers?

**The default font

for page numbers
is Calibri, size 11 ☐ ☐ ☒ ☐ ☐ ☐ ☐
even after you
have changed the
font in your paper
so make sure to
check
Spell out ☐ ☐ ☒ ☐ ☐ ☐ ☐
abbreviation at
first use if not
recognized by
AMA

***Remember
that you may
add/subtract
content with each
draft so something
that once spelled
out might be
removed and need
to spelled out
 11

again
Spell out numbers
and abbreviations
that begin a
sentence?

**If an
☐ ☐ ☒ ☐ ☐ ☐
abbreviation must ☐
be spelled out to
begin a sentence,
do not include the
abbreviation in
parentheses after
words unless this
is the first use.
Numeric values
when referring to
☐ ☐ ☒ ☐ ☐ ☐ ☐
numbers in
sentence (“3”, not
“three”)
Reference
superscripts after ☐ ☐ ☒ ☐ ☐ ☐ ☐
each sentence I
used a reference?
OAR is properly
defined as organS
at risk.

**This is a
common mistake, ☐ ☐ ☒ ☐ ☐ ☐ ☐
even in journal
publications. By
saying OARs, you
are implying
organs at risks
which doesn’t
make sense
If I directly cited an
author, did I
immediately
include the ☐ ☐ ☒ ☐ ☐ ☐ ☐
reference
superscript
following the
author’s name?
Tables and figures
are referenced in-
text directly ☐ ☐ ☒ ☐ ☐ ☐ ☐
following the
sentence (….
(Figure 1).
All terms must be ☐ ☐ ☒ ☐ ☐ ☐ ☐
 12

spelled out in the

abstract and
manuscript at first
use

**So if you refer to

and spell out
VMAT in the
abstract, you must
also define the
term again in the
manuscript
Scholarly writing is
appropriate

**Do not use ☐ ☐ ☒ ☐ ☐ ☐ ☐

terms such as max,
cord, rad onc,
simmed etc. Spell
out these terms
and avoid slang
All reference of
our profession
should be written
as “medical
dosimetrist” not
☐ ☐ ☒ ☐ ☐ ☐ ☐
just “dosimetrist.”

**Remember that
there are other
types of
dosimetrists
Is my paper
formatted
according the ☐ ☐
☐ ☐ ☒ ☐ ☐
instructions? Case
study vs. Research
Paper

Reference Page
Page break
before this ☐ ☐ ☒ ☐ ☐ ☐ ☐
section?
Capitalize the
first letter of
☐ ☐ ☒ ☐ ☐ ☐ ☐
the first word
in the title only
Abbreviate
and italicize ☐ ☐ ☒ ☐ ☐ ☐ ☐
the journal?
Year, volume, ☐ ☐ ☒ ☐ ☐ ☐ ☐
 13

issue and page

number
written
without any
spaces?

**If you didn’t

find one listed,
consider
completing
another
literature
search review.
If you cannot
find one, reach
out to
instructor for
help
Doi?

**Remember
that most
publications
have doi
numbers now
so if you do
☐ ☐ ☒ ☐ ☐ ☐ ☐
not locate one
on the original
article,
complete
another
literature
search to find
it.
Format dois
like this:
http://doi.org..
.
☐
☐ ☐ ☒ ☐ ☐ ☐
**Remember
this has
changed from
last semester
Listed in ☐ ☐ ☒ ☐ ☐ ☐ ☐
chronological
order as they
are referenced
 14

in text
Figures and Tables
Page break
before each ☐ ☐ ☒ ☐ ☐ ☐ ☐
section?
Each heading
is bolded and
☐ ☐ ☒ ☐ ☐ ☐ ☐
centered for
each section
If 2 figures are
related, they
are to be ☐ ☐ ☒ ☐ ☐ ☐ ☐
labeled as A
and B.
Captions are
written in
complete
sentences and ☐ ☐ ☒ ☐ ☐ ☐ ☐
single spaced
starting with
“Figure 1”
Figure
captions
☐ ☐ ☒ ☐ ☐ ☐ ☐
appear after
the figure
Table captions
appear before ☐ ☐ ☒ ☐ ☐ ☐ ☐
the figure
All patient
identifying
information is
☐ ☐ ☒ ☐ ☐ ☐ ☐
blocked and
fused with the
original image
All table axis,
labels and
legends are in
☐ ☐ ☒ ☐ ☐ ☐ ☐
Times New
Roman, size 12
font
Any DVHs
include
structure ☐ ☐ ☒ ☐ ☐ ☐ ☐
labels directly
on the DVH
Vertical lines ☐ ☐ ☒ ☐ ☐ ☐ ☐
are removed
 15

from tables
Single line
spacing used
for figure and ☐ ☐ ☒ ☐ ☐ ☐ ☐
table
descriptions
 16

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 purpose of this case study is to compare treatment planning techniques and
examine the precentral gyrus dose in an extreme SRT case of 36 metastatic lesions.
Case Description: Three plans were retrospectively created for a patient with 36 metastatic
lesions of the brain. The techniques used were whole brain radiotherapy (WBRT), whole brain
radiotherapy hippocampal avoidance (WBRT-HA), and stereotactic radiosurgery (SRT). The
dose to the precentral gyrus, an important neurological structure for learning and memory, was
compared between the plans.
Conclusion: Stereotactic radiotherapy yielded the lowest relative dose to the precentral gyrus
(31.6%) compared to WBRT (102.7%) and WBRT-HA (106.5%).
Key Words: Stereotactic radiotherapy, multiple brain metastases, precentral gyrus.
Introduction
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.1 The brain, unlike most organs, is an elaborate system with fundamentally and
functionally different areas. Unfortunately, with the nature of WBRT, an excessive amount of
healthy tissue is exposed to radiation, potentially 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
One neural structure which was often not contoured or constrained when planning
traditional WBRT was the hippocampus. Located deep in the temporal lobe, the hippocampus is
a sensitive neural structure which plays an instrumental role in learning and memory.3 Specific
 17

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 that were
adapted for cranial irradiation.
To keep dose to healthy tissue minimized, SRT and WBRT-HA techniques can be used
clinically for primary and metastatic brain lesions. Prior to the adaptation of SRT and WBRT-
HA, whole brain radiotherapy was the treatment method for multiple metastases and
prophylactic care, however, this method did not aim to limit dose to healthy neural structures. In
recent years, the hippocampi have been identified as radiosensitive neural structures with a
reduction in cognitive failure risk compared to WBRT when they are spared.1 Similarly, SRT is
very precise and has the potential to further reduce dose to additional neural structures other than
just the hippocampi. The benefits of SRT and WBRT-HA stem from their 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.
When treating patients that require cranial irradiation, Quantitative Analysis of Normal
Tissue Effects in the Clinic (QUANTEC) currently lists dose limits for structures such as optic
nerves, eyes, lenses, chiasm, and cochlea. For the brain itself, however, QUANTEC data is
limited, indicating constraints for whole brain tissue, brainstem, and hippocampus. 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.3 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. It runs parallel to the central sulcus on the frontal lobe, ends at the
anterior sulcus, and extends inferiorly to the lateral sulcus.5
The problem which arises 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
 18

36 metastatic brain lesions were treated with SRT compared to traditional WBRT or WBRT-HA.
The first goal of this case study was to identify the precentral gyrus dose for SRT, WBRT-HA,
and traditional WBRT. The second goal of the case study was to evaluate the necessity for SRT
according to precentral gyrus dose.
Case Description
Patient Demographic and Setup
The researchers of this case study aimed to evaluate precentral gyrus sparing for an SRT
patient who greatly exceeded 3 metastatic lesions. To be included in this case study, presentation
of 10 or more metastatic lesions was required, with at least 50% of the lesions residing superior
to the central sulcus and within the frontal lobe. Exclusion criteria included previous cranial
irradiation. 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
(Figure 1A). No previous cranial irradiation had been administered.
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
simulation included a CDR board with custom mask and cranial mold. A Philips Brilliance big
bore 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 which 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).
Of the 36 total metastases treated, 18 were of particular interest as they were located
within the frontal lobe and superior to the lateral sulcus (Figure 1B). The total volume and
distance from the precentral gyrus for each of the 18 PTVs of interest were recorded (Table 1).
 19

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 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 al1 (Table 2). All OAR constraints were met for their respective treatment modality,
and any constraint not specified by department standards followed QUANTEC guidelines.
The 2 isocenter SRT plan was designed in a way which divided the brain into anterior
and posterior halves; 1 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
optimal PTV coverage (Table 3). The energy utilized for this plan was 6 MV flattening filter-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 additional plans were generated retrospectively for comparison of precentral gyrus
dose against that which was received by the SRT treatment. 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°. The PTV for this plan was simply the
entire brain and a single isocenter was placed in the center of 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. Equal field weighting was used to distribute uniform coverage across the PTV
and dose was normalized to the midplane of the brain. Following facility protocol, field-in-field
techniques were not used. This retrospective plan was not used for treatment but was created as a
clinically treatable plan. The precentral gyrus was not intentionally blocked nor were planning
techniques used to explicitly spare the precentral gyrus; PTV coverage and OAR constraints
were met per facility standards and QUANTEC guidelines. The traditional fractionation of 30 Gy
in 10 fractions was used when creating this plan.
 20

The second retrospective 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. Optimization tools within Eclipse were utilized
to ensure OAR constraints were met. Gantry angles of 355°, 50°, 110°, 185°, 225°, and 300°
were used when planning this treatment. 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. The precentral gyrus was not intentionally blocked nor were optimization tools
used to explicitly spare the precentral gyrus; PTV coverage and OAR constraints were met per
facility standards and QUANTEC guidelines. The prescription of 25 Gy in 10 fractions used for
treatment planning was based on facility protocol for WBRT-HA plans.
Plan Analysis and Evaluation
Each plan was created using a clinically relevant prescription for that method. The results
were reported in terms of dose relative to the prescription (Table 4). Using different prescriptions
allows for a comparison of the precentral gyrus dose for each technique as they would be used
clinically. Planning target volume coverage was acceptable for all plans, and target coverage was
prioritized over neural structure sparing. All PTVs were covered with at least 98% prescription
dose, only due to proximities of OAR. Specifically, the lesions close to the OAR in the WBRT-
HA plan received less than 100% due to limitations of static MLCs. The precentral gyri were not
prioritized over PTVs, including the overlapping PTVs (Table1).
Stereotactic radiotherapy yielded the lowest relative minimum, maximum, and mean
dose to the precentral gyrus. The mean dose to the precentral gyrus for SRT was 31.6% of the
prescription compared to 102.7% for WBRT and 106.5% for WBRT-HA. However, the results
demonstrated that SRT did better at avoiding the precentral gyrus, despite 2 lesions overlapping
the structure, but did worse avoiding the hippocampus, a highly critical OAR.
Whole brain radiotherapy – hippocampal avoidance had the highest relative maximum
dose to the precentral gyrus of 109.8% prescription. By comparison, WBRT had a maximum
precentral gyrus dose of 106.9%, suggesting that choosing to avoid the hippocampus may result
in increased dose to the precentral gyrus. While outside the scope of this case study, distribution
trade-offs between OAR and neural structures should be considered before applying this
information clinically.
 21

Conclusion
The precentral gyrus is rarely considered a dose limiting treatment planning structure
despite known motor and cognitive defects associated with radiation. If WBRT-HA techniques
can be used to spare the hippocampus, then it is should be possible to develop treatment methods
that can preserve other neurological structures with the intention of sparing their function. The
traditional maximum number of lesions treated with SRT is 3, but SRT has the potential to limit
unnecessary dose to critical neural structures like the precentral gyrus compared to WBRT.1 The
purpose of this study was to compare three planning techniques and examine the dose to the
precentral gyrus in a patient with 36 metastatic brain lesions.
Similar to WBRT-HA, avoiding the precentral gyrus has the potential to improve patient
quality of life. This case study showed that avoiding this structure can be done without
compromising PTV coverage. Further evaluation should assess if avoiding the hippocampus can
be done simultaneously with the precentral gyrus.
It should be noted that the prescription dose and number of fractions were different for
each method to reflect clinical doses and fractionation for each type of planning. Additionally,
the 6X-FFF energy used for the SRT plan may produce different results than 6X energy used in
the WBRT and WBRT-HA plans. Further research is needed to determine how the radiobiologic
effects differ between the methods. This study was limited to one patient and the final dose to the
precentral gyrus was dependent on the proximity of the targets to that structure. The application
of these results to the general population cannot be determined from this case study.
 22

References
1. 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
2. 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
3. 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
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.
https://doi.org/10.1016/j.clon.2015.01.007
5. Ribas GC. The cerebral sulci and gyri. Neurosurgical Focus FOC. 2010;28(2):E2-.
https://doi.org/10.3171/2009.11.FOCUS09245
 23

Figures

Figure 1. 3D model of the patient shows the precentral gyrus (A) (peach) and the target volumes
(B).
 24

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 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 50
*18 of the 36 metastatic lesions superior to the lateral sulcus
+
cc – cubic centimeter

Table 2. Dose Constraints for the Organs at Risk Utilized During Treatment Planning in Percent
of the Prescription Dose.
Structure SRT WBRT WBRT-HA
Dmax = 55.6%
Brainstem N/A Same as WBRT
V37% = 0.5 cc
Eyes Dmax = 7.4% Dmax < 110% Same as WBRT

Optic Chiasm Dmax < 56.7% Dmax < 110% Dmax ≤ 100%

Dmax < 56.7%

Optic Nerves Dmax < 110% Dmax ≤ 100%

Bilateral D100% ≤ 30%

N/a N/A
Hippocampi Dmax ≤ 54%
*Cubic centimeter (cc); Maximum dose written as a percent of the total prescription (D max); Volume receiving X%
of total prescription dose (V(X%)); 100% of the organ volume receives X% of total prescription dose (D 100% = X).

Table 3. Arc Beams, Couch Rotations, and Collimator Angles Used for Planning Stereotactic
Treatment.
 25

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. Relative Prescription Dose to the Precentral Gyrus Observed for Each Treatment
Method
Maximum % Mean %
Prescription Dose Prescription Dose
SRT 102.7 31.6
WBRT 106.9 102.7
WBRT-HA 109.8 106.5
*Centigray (cGy)