1

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 the study is to compare the heart dose for FFF and FF
DIBH field-in-field treatments for left-sided chest wall patients.

Problem Statement: The problem is increased heart toxicity for left-sided chest wall patients.

Hypotheses: The research hypothesis (H1) is that using FFF beams for a tangential chest wall
plan will reduce mean heart dose while maintaining the same coverage to the chest wall. The null
hypothesis (H0) is that using FFF beams for a tangential chest wall plan will not reduce mean
heart dose while maintaining the same coverage to the chest wall.

H1: The research hypothesis (H1) is that using FFF beams for a tangential chest wall plan will
reduce mean heart dose while maintaining the same coverage to the chest wall.
H10: The null hypothesis (H0) is that using FFF beams for a tangential chest wall plan will not
reduce mean heart dose while maintaining the same coverage to the chest wall.
 2

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: Minimizing dose to the heart in left sided post mastectomy patients by using
the field-in-field flattening filter free technique with deep inhalation breath hold

Group: 7
Reviewer’s recommendation
Author must include both the
hypothesis and null hypothesis
at the end of last paragraph for
readers
How addressed Page numbers where change
appears
Researchers tested the p.13
hypotheses (H1) that using
FFF beams for a tangential
chest wall plan will reduce
mean heart dose while
maintaining the same
coverage to the chest wall.
The null hypothesis (H0) is
that using FFF beams for a
tangential chest wall plan will
not reduce mean heart dose
while maintaining the same
coverage to the chest wall.

Fix citation Reformatted reference 4 p. 15

Define ORL O-ring linear accelerator (ORL) p. 12
Review AMA formatting for Changed the formatting to p. 12
“Barsky et al10,” Barsky et al,10
Spell out RT for first use Wrote out “radiation therapy p. 11
(RT)”
 3

Deleted “.” after each reference Removed “.” p. 13

Delete necessary suggestions in Deleted suggested grammar p. 11
the introduction section in corrections in introduction
paragraphs 1 and 2 paragraphs 1 and 2
For the patient selection section. Simplified the patient selection p. 12
Do not include prescription or paragraph to only include
other unrelated. patient-based information.
Take out “retrospective” Took out “retrospective” in p. 13
redundant places.
RTOG guideline Use UM guidelines p. 14
Beam edges non divergent removed p. 14
Need a statistical analysis Added statistical analysis p. 14
section
Add trended points that was not Added trends to discussion area p. 15
used
Edits from instructors Rearranged paragraphs p. 14-15
 4

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 Submissio Submissio Submission Submission Submission Submission Submission

n Date: n Date: Date: Date: Date: Date: Date:
6/14/202 7/5/2020 7/26/2020 8/9/2020
0

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

***Remembe
 5

r that you
may
add/subtract
content with
each draft so
something
that once
spelled out
might be
removed and
need to
spelled out
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
 6

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
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
 7

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
 8

letter of
the first
word in
the title
only
Abbreviat ☐ ☐ ☐ ☐ ☐ ☐ ☐
e and
italicize
the
journal?
Year, ☐ ☐ ☐ ☐ ☐ ☐ ☐
volume,
issue and
page
number
written
without
any
spaces?

**If you
didn’t find
one listed,
consider
completin
g another
literature
search
review. If
you
cannot
find one,
reach out
to
instructor
for help
Doi? ☐ ☐ ☐ ☐ ☐ ☐ ☐

**Remem
ber that
most
publicatio
ns have
doi
 9

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...

**Remem
ber this
has
changed
from last
semester
Listed in ☐ ☐ ☐ ☐ ☐ ☐ ☐
chronologi
cal order
as they
are
reference
d in text
Figures and Tables
Page ☐ ☐ ☐ ☐ ☐ ☐ ☐
break
before
each
section?
Each ☐ ☐ ☐ ☐ ☐ ☐ ☐
heading is
bolded
and
centered
for each
 10

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
informatio
n is
blocked
and fused
with the
original
image
All table ☐ ☐ ☐ ☐ ☐ ☐ ☐
axis,
labels and
legends
are in
Times
New
 11

Roman,
size 12
font
Any DVHs ☐ ☐ ☐ ☐ ☐ ☐ ☐
include
structure
labels
directly on
the DVH
Vertical ☐ ☐ ☐ ☐ ☐ ☐ ☐
lines are
removed
from
tables
Single line ☐ ☐ ☐ ☐ ☐ ☐ ☐
spacing
used for
figure and
table
descriptio
ns

Minimizing dose to the heart in left sided post mastectomy patients by using the field-in-
field flattening filter free technique with deep inhalation breath hold

Nicolette Sawicki, BS; Christopher Maurino, MPH; Timothy Nguyen, BS, R.T.(T); Nishele
Lenards, PhD, CMD, R.T. (R)(T), FAAMD; Ashley Hunzeker, MS, CMD; Karen Lang, MS,
CMD, R.T.(T)
 12

Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI

Introduction
Ideal radiation treatment plans optimize on delivering therapeutic dose to the target while
sparing surrounding normal tissue. Exposing normal tissue to radiation can inadvertently
increase complication risks to the patient. Left-sided post-mastectomy patients are at risk of
receiving higher doses of radiation to the heart based on the location adjacent to the chest wall.
The adjacent organs at risk (OAR), particularly the heart, make treatment planning for breast
cancer challenging.1 However, it is imperative to continue reducing heart dose for chest wall
patients for favorable long-term outcomes such as lowering recurrences and improving overall
survival.
Patients treated with whole breast radiation treatments have a higher risk of cardiac
toxicity and can later develop conditions, such as ischemic heart disease.2 According to Hont et
al,2 the 20-year predicted excess risk of death from ischemic heart disease attributable to
radiation was 3.5 excess events per 1,000 patients. Rates of major coronary events increased
linearly with the mean dose to the heart by 7.4% per Gy, with no apparent threshold.3 The
increase started within the first 5 years after radiotherapy and continued into the 3rd decade after
radiotherapy.3 Due to the risk of heart complications for left chest wall patients, the goal is to
minimize dose to the heart by any means possible. Significant advances in radiation therapy (RT)
techniques throughout the past decades, such as three-dimensional (3D) treatment planning, have
led to a continuous reduction in radiation dose to the heart.4 In conjunction with treatment
planning advances, deep inspiration breath hold (DIBH) is used for a more favorable position of
the heart during inspiration, to reduce heart dose throughout radiation therapy treatments.
Several researchers have suggested DIBH displaces the breast or chest wall away from
the heart, consequently reducing dose to the patient’s heart.5,6,7 In addition, DIBH decreases the
variable of motion with improved reproducibility to further minimize heart dose. As a result,
DIBH can decrease the mean heart dose by 25% to 67% compared with standard free breathing.6
Smyth et al7 found that DIBH can reduce the mean heart dose by 3.4 Gy compared to free
breathing. While the DIBH technique has proven to lower the heart dose with regular photon
beams, it is essential to explore additional means of heart dose reduction which may be achieved
using flattening filter free (FFF) beams.
 13

Various characteristics differentiate FFF to conventional flattening filter (FF) beams.

Flattening filter free beams have a different photon energy spectrum leading to sharper penumbra
and less out-of-field doses. Also, FFF has a higher dose rate and less head scatter properties.8
Morris et al9 researched the feasibility of using FFF beams for field-in-field technique in 10
breast cancer patients revealing that clinically desired coverage, hot spots, and overall plan
quality were comparable to plans that were already clinically delivered with breast tangents.
Flattening Filter Free beams have shown to be effective in planning target volume (PTV)
coverage while also decreasing the overall treatment time. Barsky et al10 demonstrated that a 6X-
FFF O-ring linear accelerator (ORL) could be used across most clinical scenarios to treat
patients with breast cancer. Using the FFF technique has the potential to lower heart dose with
the sharper dose fall off, possibly changing the standard of care for optimal treatment of left-
sided chest wall patients using DIBH.
Previous research indicated the need to reduce heart dose for left-sided chest wall
patients. The use of DIBH has proven to be beneficial in displacing the heart and decreasing the
dosage. However, the problem of increased heart toxicity remains for left-sided chest wall
patients. The FFF field-in-field technique has the potential to minimize heart dose to left-sided
chest wall patients. Therefore, the purpose of this study is to compare the heart dose for FFF and
FF DIBH field-in-field treatments for left-sided chest wall patients. Researchers tested the
hypotheses (H1) that using FFF beams for a tangential chest wall plan will reduce mean heart
dose while maintaining the same coverage to the chest wall.

Methods and Procedures

Patient Selection
Twelve patients from a single radiation oncology system were selected for this
retrospective study. The inclusion criteria included females treated with left-sided chest wall
field-in-field 3-dimensional radiation therapy (3DRT) and DIBH. Patients were not excluded
based on lymph node involvement. Dose from the scar boost was not considered in this
comparison.
The breath threshold was used in simulation, treatment planning and treatment delivery.
Each patient was simulated using a Philips Brilliance Big Bore CT Scanner. The patients were
positioned head-first supine with both hands above the head, utilizing a breast board. Radio-
 14

opaque markers were placed at the superior, inferior, lateral, and medial borders by the radiation
oncologist to indicate the treatment area.
Contours
The CT scan was exported to the Aria Eclipse (Version 15.6) treatment planning system
(TPS) for treatment planning and contouring of OAR and target structures. A Certified Medical
Dosimetrist (CMD) manually contoured the chest wall, heart, and left lung according to
University of Michigan department guidelines. A 0.2 cm bolus was included in the body contour
for dose calculations and used for daily treatment of the chest wall tangential fields. The
radiation oncologist manually contoured the internal mammary lymph nodes (IMN), level 1
axillary lymph nodes, level 2 axillary lymph nodes, level 3 axillary lymph nodes, supraclavicular
lymph nodes and planning target volume (PTV) that is 0.5 cm away from the skin surface.
Treatment Planning
Planning was completed using Eclipse with field-in-field technique on approved and
treated left-sided chest wall breast cancer, utilizing DIBH with the SDX system. The gantry
angles varied but were patient-specific to include the chest wall, avoid entrance and exit dose in
the contralateral chest wall, and block the lung and heart to minimize the amount of lung and
cardiac dose. For some patients, the radiation oncologist manually set treatment fields and
cardiac shielding. However for other patients, the treatment fields, were established by a medical
dosimetrist, and the radiation oncologist was responsible for ensuring correct gantry angle,
cardiac shielding, and field shape before treatment approval. During retrospective re-planning,
the gantry angles, collimator angles, and cardiac shielding were not faltered. Six and 16 MV
energies were used depending on patient thickness. Also, the use of a posterior axillary boost
was patient-specific. The supraclavicular field and supraclavicular dose were not changed in this
study.
The treated plans were designed using a field-in-field treatment technique using 6 MV FF
beams. Segments of the 6 MV FF plans used the field-in-field method to decrease hot spots and
uniformly treat the chest wall. The segments were required to be different due to FFF's beam
profile, which would not allow the same field arrangements. Dose calculations were performed
with Anisotropic Analytical Algorithm Version 15.6.05. The patients were designed to assess the
dose on a Varian TrueBeam Linear accelerator. The plans were then optimized until nearly
identical for PTV coverage to the previously treated plan.
 15

Plan Comparison
A plan comparison was performed between the new and previously treated plans. Dose
constraints were based on the Michigan Radiation Oncology Quality Consortium (MROQC).11
The mean heart dose was analyzed for each patient. From the twelve patients, the standard
deviation, mean dose, and variance was obtained for FFF and FF plans (Table 1).
Statistical Analysis
Each plan was evaluated individually to collect data for this study and compared to
previously approved plans. one-sided Wilcoxon signed rank tests (WSR) were performed to
compare the distributions for the FFF and FF planning techniques. The WSR was performed for
mean heart dose. With a family-wise error rate of 5% for each OAR, the Benjamini-Hochberg
adjustment, or false discovery rate, was applied to control the type 1 error rate for multiple
testing. Statistical analysis was performed using R from R Core Team. Wilcoxon signed rank
tests were used rather than paired t-tests due to small sample sizes and outliers observed in some
of the samples. Significance level, alpha (α), is the probability of rejecting the null hypothesis
when it is true. A significant level of 0.05 indicates a 5% risk of concluding that a difference
exists when there is no actual difference.

Results
Mean heart dose
To investigate the relationship between using FFF and mean heart dose, a one sided
Wilcoxon signed rank test was performed. The distribution for heart mean dose is significantly
lower for the population of patients where planning was done using FFF than for FF (P <
0.0005). Figure 1 shows a boxplot for the differences along with a reference line at 0 for
comparison (Figure 1). Positive values indicate that the dose when using FF is greater than for
FFF. At α=0.05, there is sufficient evidence to conclude that using FFF beams for a tangential
chest wall plan will reduce mean heart dose while maintaining the same coverage to the chest
wall, and the null hypothesis was rejected.
Discussion
The results of the current analysis demonstrated that using 6FFF beams would reduce
dose to the heart. Conventionally, FFF beams have not typically been used in 3D planning due to
the insufficient ability to deliver homogenous dose to targets. However, the target coverage was
not compromised, and there was an improvement in the mean heart dose. Barsky et al.4
 16

demonstrated similar findings in a study of treating patients with breast cancer on a 6-MV FFF to
reduce heart toxicity. Each plan met MROQC and institutional DVH constraints for target
coverage and OAR sparing for nearly all plans, even with the inclusion of DIBH. Research has
shown that treatments that utilized DIBH were useful in displacing the heart to decrease the dose.
It has been suspected that radiation therapy of left-sided breast cancer might lead to
relevant cardiac toxicities. In early trials including breast RT, an increase in the number of
cardiac deaths was observed, and cardiac mortality was higher in left-sided breast cancer patients
than in right-sided disease.4 A study showed that for every Gy the mean dose to the heart is
increased, the risk for ischemic heart disease increases by 7.4%.3 By using the FFF technique, it
allowed for a sharper dose fall off, which allowed for less dose to surrounding OAR. Other
trends noticed in this research were heart Dmax and left lung dose, but further research would be
needed to determine significance. The current research confirmed that left-sided breast treatment
plans can be improved with minimal changes to the planning process by using FFF beams with
DIBH.
Conclusion
The purpose of this retrospective study was to determine if there was a difference when
using FFF DIBH field-in-field treatments for left-sided chest wall patients to reduce heart
toxicity while maintaining target coverage. The use of FFF beams was shown to reduce dose to
the heart. Therefore, there was a significant correlation between using the FFF DIBH technique
and heart dose. The mean heart dose was found to be statistically significant (P < 0.05). Also, all
plans maintained the same planning directives and adequate coverage as the original plans.
The limitations of this study included data collection at a single institution using one TPS
and algorithm. Utilizing multiple institutions could provide a more extensive range of results and
population to determine more of a significance. Additionally, this research could be completed
using different TPS algorithms or linear accelerators for the same anatomical site to see if the
same results would be presented. The use of a larger patient population could also be used to
determine the significance of this research. Further research may evaluate the different OAR on
the left side of the patient, for instance, lung dose.
 17

References
1. Hu J, Han G, Lei Y, et al. Dosimetric comparison of three radiotherapy techniques in
irradiation of left-sided breast cancer patients after radical mastectomy. BioMed Res Int.
2020;2020:1-10. http://doi.org/10.1155/2020/7131590
2. Hong JC, Rahimy E, Gross CP, et al. Radiation dose and cardiac risk in breast cancer
treatment: an analysis of modern radiation therapy including community settings. Pract
Radiat Oncol. 2018;1-3. http://doi.org/10.1016/j.prro.2017.07.005
3. Darby SC, Ewertz M, Mcgale P, et al. Risk of ischemic heart disease in women after
radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-998.
http://doi.org/10.1056/nejmoa1209825
4. Piroth MD, Baumann R, Budach W, et al. Heart toxicity from breast cancer radiotherapy.
Strahlenther Onkol. 2018;195(1):1-12. http://doi.org/10.1007/s00066-018-1378
5. Sripathi L, Ahlawat P, Simson D, et al. Cardiac dose reduction with deep-inspiratory
breath hold technique of radiotherapy for left-sided breast cancer. J Med Phys
2017;42(3):123. http://doi.org/10.4103/jmp.jmp_139_16
6. Bergom C, Currey A, Desai N, Tai A, Strauss JB. Deep inspiration breath hold:
techniques and advantages for cardiac sparing during breast cancer irradiation. Front
Oncol. 2018;8. http://doi.org/10.3389/fonc.2018.00087
7. Smyth LM, Knight KA, Aarons YK, Wasiak J. The cardiac dose‐sparing benefits of deep
inspiration breath‐hold in left breast irradiation: a systematic review. J Medical Radiat
Sci. 2015;62(1):66-73. http://doi.org/10.1002/jmrs.89
8. Xiao Y, Kry SF, Popple R, et al. Flattening filter-free accelerators: a report from the
AAPM Therapy Emerging Technology Assessment Work Group. J App Clin Med Phys.
2015;16(3):12-29. http://doi.org/10.1120/jacmp.v16i3.5219
9. Morris R, Laugeman E, Hilliard J, et al. Field‐in‐field breast planning for a jawless,
double‐stack MLC LINAC using flattening‐filter‐free beams. J Appl Clin Med Phys.
2019;20(11):14-26. http://doi.org/10.1002/acm2.12722
10. Barsky AR, Ogrady F, Kennedy C, et al. Initial clinical experience treating patients with
breast cancer on a 6-MV flattening-filter-free O-ring linear accelerator. Adv Radiat
Oncol. 2019;4(4):571-578. http://doi.org/10.1016/j.adro.2019.05.006
 18

11. Pierce LJ, Feng M, Griffith KA, et al. Recent time trends and predictors of heart dose
from breast radiation therapy in a large quality consortium of radiation oncology
practices. Int J Radiat Oncol Biol Phys. 2017;99(5):1154-1161.
https://doi.org/10.1016/j.ijrobp.2017.07.022
 19

Tables

Table 1. Standard deviation, sample size, mean, and variance for 6FFF and 6FF mean heart dose
6FFF 6FF
Standard Deviation 0.22943111463713 0.23385439655452
Count, N: 12 12
Mean (Gy), x̄: 1.118 1.251
Variance, s2: 0.052638636 0.054687879

Figures

Figure 1. Boxplot of the reduction in heart mean dose showing how much lower the dose is
using FFF than with FF DIBH field-in-field treatments for left-sided chest wall patients.