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Radiation therapy treatment of the prone breast using EZFluence: A case study

ABSTRACT
This study considered 2 separate radiation treatment planning techniques for prone breast
irradiation: the traditional field-in-field (FiF) technique and the EZFluence planning technique.
Differences between the overall treatment planning time, the amount of the planning target
volume (PTV) receiving ≥ 105 percent of the dose (V105), as well as dose to the organs at risk
(OAR) and nearby critical structures were taken into account. Ten patients were planned
retrospectively to include the whole affected breast to a dose of 42.56 Gy using both non-
divergent medial and lateral 3-dimensional conformal radiation therapy (3D CRT) tangential
beams produced by both manual FiF techniques and EZFluence software. For the FiF technique,
maximum dose regions were blocked until the 104% isodose line, while also removing as much
as the 105% isodose line throughout the breast volume. Appropriate coverage was maintained to
the targets. The EZFluence technique involved the user creating plans using the software script
accessed through the Eclipse treatment planning system (TPS), which generated optimal fluences
and calculated dose. The EZFluence FiF were also manipulated until as much of the V105 was
removed as possible, while keeping the appropriate coverage to the targets. All plans were
generated with the goal of achieving at least 95% of the whole breast PTV_Breast_Eval and the
PTV_Lumpectomy_Eval structures receiving at least 95% of the prescription dose. Results were
reviewed which showed a marked improvement by using the EZFluence technique over manual
FiF techniques when comparing overall treatment planning time and the amount of V105. Dose
amounts to the OAR were slightly elevated when using the EZFluence script, as compared to the
manual FiF technique, while adequate coverage to the target was achieved by both.

Introduction
Breast cancer has remained the most commonly diagnosed cancer in women worldwide,
and the fifth leading cause of death from cancer overall.1 Historically, several methods have been
utilized for treating breast cancer including surgical resection, chemotherapy, and radiation
therapy or a combination of approaches. In recent times, new techniques and technologies have
advanced treatment planning as well as treatment delivery, specifically within the area of
radiation therapy. One such technique, that has proven to be effective, is radiation therapy
treatment delivery to the breast with the patient in the prone position. Another potentially useful
practice came in the form of a software script known as EZFleunce, which offers help to
dosimetrists by claims of faster treatment times and more uniform dose distribution.
Since its inception, several independent studies have recognized the benefits of whole
breast irradiation in the prone position in treating breast cancer.2,3 Benefits to treating breast
cancer in the prone position include, but are not limited to, decreasing acute toxicity, risks of
radiation induced lung cancer, and cardiac toxicity.2 The cosmetic benefits to prone treatments
have proven to be very effective as well, due to the breast being able to hang away from the
patient’s chest, which helps to alleviate the creation of skin folds thus stopping the bolus effect
seen in supine treatments. In fact, Olson4 reported that only 4.5 percent of breast patients treated
prone had Grade 3 skin reactions and a 22 to 36 percent higher cosmetic outcomes when
compared to patients treated supine. Research done by Haffy,3 has also suggested additional
benefits to prone breast radiotherapy, such as improved dose coverage, better homogeneity, less
areas of maximum dose within the treatment volume, lower heart and ipsilateral lung dose, lower
contralateral breast dose, and reduced skin reactions.
While setup position for breast radiotherapy is one factor that affects dose to the target
and surrounding organs at risk (OAR), the ability to reduce dose inhomogeneities is another vital
aspect to minimizing patient toxicities. As a means to help achieve these aforementioned benefits
of the prone position, multiple planning techniques have been utilized over the years, such as
physical wedges, enhanced dynamic wedges, manual field-in-filed (FiF), electronic
compensators, and intensity modulated radiation therapy (IMRT). As another way to aid in
breast treatment planning, one new software has been developed, known as EZFluence, which
can be used to create an optimal fluence pattern in order to generate a homogenous dose
distribution for breast irradiation treatments.5
Even with the use of better positional methods and FiF techniques or planning software,
dosimetrists have continued to face several struggles when creating treatment plans. One struggle
that dosimetrists face has been the speed and consistency in which plans are generated, which
has been a problem, and continues to be a problem for even the best dosimetrists.6 It can take up
to several hours to accurately plan and calculate complicated 3-dimensional conformal radiation
therapy (3D CRT) breast plans.6 Any improvement to the treatment planning time would help by
giving the dosimetrist more time to focus on additional cases and plans, thus increasing
productivity.
Another struggle that dosimetrists have faced when planning 3D CRT prone breast
radiotherapy treatments has been producing fields with an even dose distribution while
maintaining a low amount of breast tissue receiving greater than plus 5 percent of the
prescription amount. Dosimetric inhomogeneity in breast treatment planning, specifically in
breast volumes treated to ≥ 105 percent of the prescribed dose, has been a proven predictor of
long-term breast pain.7 Based on their research, Keenan et al8 found that in cases when the
volume of the breast receiving ≥ 105 percent (V105) ≥ 30cc with conventional fractionation have
a strong indicator for acute skin toxicity in general breast planning. Another study by Hymas et
al,9 proved that by reducing the V105 to ≤ 10 percent of the overall breast volume would achieve
excellent or good cosmesis following radiotherapy to the breast, as well as acceptable level of
toxicity. Due to the increased risk of skin toxicity, maximizing dose homogeneity and reducing
inhomogeneities involving the region of V105 have become an important planning criterion to be
evaluated when generating treatments.
Sparing of OAR has also been a longtime concern with most any treatment planning
technique, with prone breast radiotherapy being no exception. In prone breast cases, the OAR of
interest typically includes organs such as the heart, ipsilateral lung, and liver. The most drastic
differences using the prone technique in breast cancer patient treatment planning can be seen in
the dose amount to the heart and ipsilateral lung. This was demonstrated through a study by
Venkatesan et al,10 which showed that treating breasts in the prone position would lower both the
volume and the dose exposure to the lungs, though there was no real statistical difference in
mean heart dose on left sided breast cancer treatments. Even with positional improvements to
minimize the dose to critical structures and OAR, attaining a homogenous plan with adequate
dose to the tumor volume continues to be a challenge.
The utilization of both FiF techniques and software scripts, such as EZFluence, have
helped dosimetrists with planning difficulties discussed above. Field-in-field techniques have
been recognized as an effective means of controlling these problems. To date, however, there has
been very limited data demonstrating the benefits of EZFluence as compared to manual FiF
techniques for supine and prone breast patients.5 The results of one study, which sought to
demonstrate the usefulness of the EZFluence software script, found that EZFluence was able to
greatly improve treatment planning time, reduce the volume of planning target volume (PTV)
receiving V105, and achieve similar dose constraints to the OAR.
The purpose of our study was to provide information on the use of the EZFluence
software script to determine if it would help improve prone breast planning time, OAR sparing,
and overall dose uniformity to the target. Based on positional reasoning behind breast treatment
planning in the prone position, as well as dose uniformity and OAR constraints, the metrics for
this study were formed to demonstrate if these measures could be improved by using the
EZFluence software script over conventional FiF techniques. The main qualities examined by
this study were overall treatment planning time, the amount of V105 within the plan, and the
ability to meet dose constraint criteria placed on the OAR.

Case Description
Patient Selection
Patient selection was based on various factors and narrowed to a study group of 10
female individuals with breast cancer who met the criteria. For this study the criteria included
female patients with intact, pendulous breasts (post-lumpectomy) without nodal involvement.
Only patients that were set up in the prone position, per the attending radiation oncologist’s
request, were included. The range of the PTV size for our included patients was 547-1090 cc; the
mean PTV size was 860 cc.
Planning was done retrospectively to include the whole affected breast to a dose of 42.56
Gy using both non-divergent medial and lateral 3D CRT tangential beams produced by both
manual FiF techniques and EZFluence software. Additional dose from any boost prescribed after
the initial 42.56 Gy was not included in this study.
All 10 patients received a CT simulation with a General Electronic (GE) Lightspeed 16
multi-slice CT scanner. All patients were setup in the prone position on a CDR Systems prone
breast board with their arms up prior to treatment planning. Breast borders and the lumpectomy
scar were delineated with radiopaque wire stickers per the radiation oncologist. Alignment
reference markers were used for positioning and subsequent markings were placed for future set-
up. An example of the CT simulation setup devices as well as the patient positioning that were
used can be viewed in Figures 1a and 1b.
Isocenter was chosen by the attending radiation oncologist at the time of CT simulation
and was located at the approximate center of the breast volume (roughly at the midpoint of the
breast tissue external separation and in proximity of the chest wall). Patients excluded from this
study were those which were CT simulated in a supine position regardless if the scan was
performed with or without bolus.

Target Delineation
All target delineation was performed in Varian Medical Systems Eclipse treatment
planning system (TPS), version 15.6. Targets were delineated for treatment planning by the
medical dosimetrists and the attending radiation oncologist to ensure accuracy and consistency.
The general OAR for prone breast treatment planning were contoured as well, which included
the bilateral lungs, heart, liver, and spinal cord. Contouring of the OAR was performed per the
Radiation Therapy Oncology Group (RTOG) contouring atlas recommendations. Target volumes
including PTV structures and the lumpectomy cavity were then delineated (Figure 2).

Treatment Planning
The CT scans of the 10 patients in this study were imported from CT simulation to the
Eclipse TPS. Each patient was prescribed a radiation dose of 42.56 Gy to the intact whole breast
delivered in 16 fractions at 2.66 Gy per fraction. Medical dosimetrists planned the cases for
consistency in technique. The radiation oncologist placed radiopaque wire stickers at the time of
CT simulation on the patient’s midsagittal plane and approximately 2.0 cm beyond the palpable
breast tissue in the superior, inferior, and lateral aspects. These wires were used to determine the
approximate breast tissue borders and assist in defining beam angles, collimator angles, and field
sizes during treatment planning. To ensure adequate anterior coverage to the breast tissue, a 2.0
cm margin beyond the breast tissue was included anteriorly in air. Two fields were tangentially
aligned to the PTV to create non-divergent opposed fields. Two different 3D CRT plans were
created for each patient, one utilizing the manual FiF technique and the other using EZFluence
software. All plans were constructed using opposed non-divergent tangential field arrangements
with 6 MV photon energy beams.
For the manual FiF treatment plans, the initial fields included open multileaf collimator
(MLC) leaves for the medial and lateral tangent fields. A reference point was placed within the
field, and the plan was normalized so that upon calculation, 100% of the prescription dose was
delivered to that point. The 107% dose cloud was turned on to verify that the reference point was
not placed within the 107% dose cloud. The field weightings were adjusted slightly to achieve a
uniform dose distribution to the PTV_Lumpectomy_4256. At the dosimetrist’s discretion, the
collimator was rotated 90 degrees in order to allow for optimal blocking with the MLC leaves.
The dosimetrist manually created the field-in-fields every 2% until the 104% isodose line was
reached. These were between 2 to 4 subfields per gantry angle. The FiF weighting was still set to
0% at this point. Starting with the first FiF, the maximum dose was blocked at every 2% interval
utilizing the MLC leaves. The reference point was not blocked by any of the MLC leaves. The
process of blocking the maximum dose regions continued until the 104% isodose line, while also
removing as much as the 105% isodose line throughout the breast volume but keeping
appropriate coverage to the targets. Each subfield was weighted 2% of the total weight. This was
done by removing the dose contribution to the original field and distributing it to the respective
subfields.
The EZFluence plans were created using the software accessed through the Eclipse TPS.
The EZFluence plans utilized the same structure sets and the primary open tangent fields as in
the manual FiF plans. There was no plan normalization enabled. EZFluence creates a
PTV_EVAL_EZ structure on the patient to calculate the initial fluences. The target was formed
with the guidelines found in Figure 3.
All plans were generated with the goal of achieving at least 95% of the whole breast
PTV_Breast_Eval and the PTV_Lumpectomy_Eval structures receiving at least 95% of the
prescription dose. The initial dose was calculated using a grid size of 0.25 cm with the analytical
anisotropic algorithm (AAA) from Eclipse TPS. In order to equally compare both the manual FiF
and EZFluence plans, the EZFluence plan was normalized so that 100% of the prescription dose
covered the same volume of the PTV_Breast_Eval (V100) as in the manual FiF plan. This was
performed on a patient-by-patient basis, which was then analyzed across the entire 10 patients in
this study.
Dose volume histogram parameters were evaluated and the planning measures of the 2
different techniques were compared. The values assessed were the amount of the PTV receiving
≥ 95% of the prescribed dose, the volume of the breast receiving 105% prescription dose, as well
as the aforementioned dose metrics to the ipsilateral lung, heart, liver, and spinal cord.
Results
Data for both the manual FiF technique plans and EZFluence generated plans were
compiled for all 10 patients. To ensure an accurate comparison between planning techniques, the
EZFluence plans were normalized using the aforementioned methods. Dose distributions and
planning metrics were evaluated based on DVH analysis. Illustrated in Figure 4 are the
generalized results of the two different planning techniques, which indicated relatively similar
outcomes in terms of OAR sparing and target coverage. The volume of breast receiving ≥ V105
and total planning time was noticeably improved using the EZFluence planning technique.
Treatment planning constraints for the heart, ipsilateral lung, liver, and spinal cord were
all achieved. However, dose to these OAR was greater in nearly every instance with the
EZFluence method. This minimal increase was not of great clinical significance [p-value =___ ]
due to the inherent ability of prone patient positioning to reduce dose to nearby OAR as
compared to supine breast positioning.2,3 The volume of the PTV_Lumpectomy_Eval as well as
the PTV_Breast_Eval receiving ≥ 95% of the prescription dose was very similar. While coverage
to the target structures was much alike, the plans generated with EZFluence produced less V105
as compared to the manual FiF method. This reduction in V105 also contributed to a lower
global maximum dose within the breast tissue. The normalized EZFluence plans averaged over a
1% reduction in global maximum dose as compared the manual FiF technique. The overall
treatment planning time was vastly improved with the EZFluence plans, with an average of over
62% in time saved (Figure 5). Much of the time saved was a result of the software’s ability to
quickly generate the necessary FiF MLC arrangements while reducing the need to remove
remaining areas of high dose.

Conclusion
Based on the results of this case study, running the EZFluence script, as opposed to using
a manual FiF technique, produced a marked improvement in the overall time needed to plan
treatment for breast patients in the prone position. Treatment planning time averaged 40.7
minutes when planning with a manual FiF technique and 15.4 minutes when using EZFluence,
which was a 62% decrease. When comparing the percentage of V105 within the plan, there was
also a significant decrease when using EZFluence over a manual FiF technique, which measured
1.75 cc and 9.99 cc respectively. Utilizing the EZFluence script also proved effective at
controlling dose to OAR with only a minimal increase to segmented structures, while still
maintaining adequate coverage to the PTV_Breast_Eval structure. These findings confirmed the
usefulness of EZFluence in breast cancer treatment planning, and furthermore demonstrated that
it can be useful on patients in the prone position as well. The main limitation to this study was
the small sample size, yet the results for each of the 10 patients were consistent across all the
measured constraints that were applied. EZFluence has proven to be a viable choice when it
comes to the treatment planning of prone breast patients, however, additional research and
evaluation should be conducted to prove its usefulness in plans other than breast cases.
References
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Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer.
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2. Boute B, De Neve W, Speleers B, et al. Potential benefits of crawl position for prone
radiation therapy in breast cancer. J Appl Clin Med Phys. 2017;18(4):200–205.
https://dx.doi.org/10.1002/acm2.12118
3. Haffty, BG. Supine or prone breast radiation: Upsides and downsides. Int J Radiat Oncol
Biol Phys. 2018;101(3):510-512. https://dx.doi.org/10.1016/j.ijrobp.2018.03.023
4. Olson KN. Improving treatment outcomes of breast radiation therapy: the prone position.
Radiat Therapist. 2014;23(1):21-26. https://web-b-ebscohost-
com.libweb.uwlax.edu/ehost/pdfviewer/pdfviewer?vid=7&sid=6c25b527-3254-4499-9769-
da885b9aa3d5%40sessionmgr102. Published Spring 2014. Accessed May 31, 2019.
5. Yoder T, Hsia AT, Xu Z, Stessin A, Ryu S. Usefulness of EZFluence software for
radiotherapy planning of breast cancer treatment. Med Dosim. 2019;S0958-3947(18):30137-
7. https://dx.doi.org/10.1016/j.meddos.2018.12.001
6. Bolan C. Expediting the treatment planning process. Appl Radiat Oncol. 2013;2(4):19-23.
http://cdn.agilitycms.com/applied-radiation-oncology/ARO_12-13_TechTrends.pdf.
Published Winter 2013. Accessed July 11, 2019.
7. Mak KS, Chen YH, Catalano PJ, et al. Dosimetric inhomogeneity predicts for long-term
breast pain after breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2014;93(5):1087-
1095. https://dx.doi.org/10.1016/j.ijrobp.2014.05.021
8. Keenan LG, Lavan N, Dunne M, McArdle O. Modifiable risk factors for acute skin toxicity
in adjuvant breast radiotherapy: Dosimetric analysis and review of the literature. Med
Dosim. 2019;44(1):51-55. https://dx.doi.org/10.1016/j.meddos.2018.01.004
9. Hymas RV, Jawad MS, Mangona VS, et al. Dosimetric predictors of toxicity and cosmesis in
women treated with hypofractionated whole-breast irradiation. Int J Radiat Oncol Biol Phys.
2014;90(1):S270-S271. https://dx.doi.org/10.1016/j.ijrobp.2014.05.930
10. Venkatesan K, Deshpande S, Anand V, et al. Comparison of heart and lung doses in deep
inspiration breath hold radiation therapy and prone position radiation therapy for whole
breast radiation therapy. Int J Radiat Oncol Biol Phys. 2018;102(3):489-490.
https://dx.doi.org/10.1016/j.ijrobp.2018.07.1393
11. Mamounas E, White J, Khan A, et al. A randomized phase III clinical trial evaluating post-
mastectomy chestwall and regional nodal XRT and post-lumpectomy regional nodal XRT in
patients with positive axillary nodes before neoadjuvant chemotherapy who convert to
pathologically negative axillary nodes after neoadjuvant chemotherapy. NRG Oncology.
Published January 11, 2013. Accessed July 14, 2019.
12. White J, Tai A, Arthur D, et al. Breast cancer atlas for radiation therapy planning: Consensus
definitions. Radiation Therapy Oncology Group (RTOG). In: RTOG Breast Cancer
Contouring Atlas. Retrieved from:
https://www.rtog.org/LinkClick.aspx?fileticket=vzJFhPaBipE=.
Figures

Figure 1a: Diagram of CT simulation setup devices / patient position.

Figure 1b: Diagram of CT simulation setup devices, patient position, and setup markings
Target Structure Determining Factors
1. Cavity Contour using all available clinical and radiographic
information including the excision cavity volume,
architectural distortion, lumpectomy scar, seroma and/or
extent of surgical clips

2. PTV_Lumpectomy_4256 Cavity + 1.0 cm expansion

3. PTV_Lumpectomy_Eval Since a substantial part of the Lumpectomy PTV often


extends outside the patient (especially for superficial cavities),
the Lumpectomy PTV is then copied to a Lumpectomy PTV
Eval which is edited. This Lumpectomy PTV Eval is limited
to exclude the part outside the ipsilateral breast and the first 5
mm of tissue under the skin (in order to remove most of the
build-up region for the DVH analysis) and excluding the
Lumpectomy PTV expansion beyond the posterior extent of
breast tissue (chestwall, pectoralis muscles, and lung) when
pertinent. The lumpectomy PTV should not cross midline

4. PTV_Breast Considers reference clinical breast at time of CT. This


includes the apparent CT glandular breast tissue and
incorporates consensus definitions of anatomical borders.
The breast PTV includes the lumpectomy cavity. It is limited
posteriorly to the anterior surface of the pectoralis, serratous
anterior muscle excluding chestwall, boney thorax, and lung.
In general, the pectoralis and/or serratous anterior muscles are
excluded from the Breast PTV unless clinically warranted by
the patient’s pathology

5. PTV_Breast_Eval The Breast PTV Eval is intended to exclude the portion of the
Breast PTV that extends outside the patient. The Breast PTV
is copied to a Breast PTV Eval which is edited. This Breast
PTV Eval is limited anteriorly to exclude the part outside the
patient and the first 5 mm of tissue under the skin (in order to
remove most of the build-up region for the DVH analysis)

Figure 2: Definition of target structures.11,12


PTV_EVAL_EZ Target Guidelines
Cropped 0.5 cm from the defined body surface
Cropped 0.5 cm from the field edges
Cropped 0.5 cm from identified OAR structures (Lung, Heart, Spinal
Cord)
Figure 3: Planning target volume structure guidelines.

Structure Volume Receiving (Dose)

Ipsilateral Lung ≥ 16 Gy (V16) ≤ 10%


≥ 8 Gy (V8) ≤ 15%
≥ 4 Gy (V4) ≤ 25%

Liver Mean Dose (Dmean) ≤ 2.8 Gy

Spinal Cord Dmax ≤ 50 Gy (used for reporting purposes)

Heart Dmean ≤ 3.2 Gy and Dmax ≤ 16 Gy


Figure 4: Dose constraints for OAR and critical structures.

Heart
Heart
(Right Lung V95% Planning
Planning (Left Side V105
Side (Mean PTV_Breast_Eval Time
Technique Treatment (cc)
Treatment - cGy) (cc) (Minutes)
- cGy )
- cGy)
Manual
249.82 493.4 59.45 9.99 95.55 40.7
FiF
EZFluence 254.9 518.4 61.07 1.75 95.97 15.4
% Change
2.0% 5.1 % 2.7% 82.5% 62.2%
for 0.4% Increase
Increase Increase Increase Decrease Decrease
EZFluence
Figure 5: Comparison on mean OAR and target dose, V105, and planning time for manual FiF
and EZFluence techniques.

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