1

Minimizing Heart Dose in Left Chest Wall Patients using FIF Flattening Filter Free with
DIBH
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); Sabrina Zeiler, MS, CMD, RT(T); Ashley Fellows, MS, CMD, RT(T)
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI
Abstract
Heart toxicity is a frequent concern when treating left sided post mastectomy patients. The
purpose of this retrospective study was to compare the heart dose for treatments planned with
flattening filter free (FFF) and flattening filter (FF) beams using deep inspiration breath hold
(DIBH) field-in-field (FIF) technique. Twelve patients who have previously been treated with a
physician approved plan using a FIF 3-dimensional method were selected and re-planned with
the use of FFF beams. The same clinical objectives were used, and the mean heart dose was
evaluated while maintaining similar planning target volume (PTV) coverage. Dosimetric data
was evaluated as well as the mean dose to the heart using the Wilcoxon Signed Rank test. All
statistical analysis was performed using R from R Core Team. The mean heart dose was
significantly lower for the population of patients planned with FFF than with FF (P < 0.0005).
Therefore, there was a significant correlation between using the FFF DIBH technique and
lowering mean heart dose.

Keywords: Radiotherapy, Cardiotoxicity, Flattening Filter Free, Deep Inspiration Breath Hold,
Breast Irradiation, Heart Dose
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Introduction
Ideal radiation treatment plans optimize 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 its location adjacent to the chest wall
which make treatment planning for breast cancer challenging.1 However, due to potential future
heart complications, it is imperative to continue reducing heart dose for chest wall patients to
provide favorable long-term outcomes.
Patients treated with whole breast radiation have a higher risk of cardiac toxicity
compared to patients not treated with radiation and can later develop conditions such as ischemic
heart disease.2 According to Hong et al2 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 following 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. 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 According to Bergom et al6 and
Smyth et al,7 DIBH decreases the variability of motion with improved reproducibility to further
minimize heart dose. When compared to free breathing, it can reduce the mean heart dose by 3.4
Gy.7 While the DIBH technique has proven to lower the heart dose with traditional photon
beams, it is essential to explore additional means of heart dose reduction which may be achieved
using flattening filter free (FFF) beams.
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 dose. Additionally, FFF has a higher dose rate and less head scatter
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properties.8 Morris et al9 researched the feasibility of using FFF beams for field-in-field (FIF)
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
traditional breast tangents. Flattening filter free beams have shown to be effective in planning
target volume (PTV) coverage while also decreasing the overall treatment time.10 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
cardiac dose. However, the problem of increased heart toxicity remains for left sided chest wall
patients. The FFF FIF technique has the potential to minimize heart dose for left sided chest wall
patients. Therefore, the purpose of this study is to compare the heart dose for FFF and FF DIBH
FIF treatments for left sided chest wall patients. Researchers tested the hypotheses (H1A) 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 selection criteria included females treated with left sided chest wall FIF
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 hold threshold was determined in simulation and replicated for 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-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 Eclipse (Version 15.6) treatment planning system (TPS) for
treatment planning and contouring of OAR and target structures. A certified medical dosimetrist
manually contoured the chest wall, heart, and left lung according to University of Michigan
department guidelines. A 0.2 cm custom bolus was included in the body contour for dose
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calculations and to cover the chest wall for daily treatment. The radiation oncologist manually
contoured the internal mammary lymph nodes (IMN), levels 1-3 axillary lymph nodes,
supraclavicular lymph nodes and planning target volume (PTV) that was cropped 0.4 cm from
the skin surface.
Treatment Planning
Treatment planning was performed using Eclipse of Varian TrueBeam linear accelerator
with FIF technique on approved and treated left sided chest wall breast cancer patients, utilizing
DIBH with the SDX system. The SDX system is a voluntary breath hold device to stabilize
tumors affected by breathing motion during x-ray imaging and radiation therapy. The beam
arrangement was created using 2 fixed tangential fields. The gantry angles selected were patient-
specific to include the chest wall, avoid entrance and exit dose in the contralateral chest wall, and
avoid the lung and heart to minimize 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 generated by a medical dosimetrist and the radiation oncologist was
responsible for verifying optimal gantry angle, cardiac shielding, and field shape before
treatment approval. During retrospective re-planning, the gantry angles, collimator angles, and
cardiac shielding were not altered. Six and 16 MV energies were used depending on patient
anatomy. Also, the use of a posterior axillary boost was patient-specific. The supraclavicular
field and dose were not changed in this study.
The treated plans were designed using a FIF treatment technique using 6 MV FF beams.
Segments of the 6 MV FF plans used the FIF method to decrease hot spots and uniformly treat
the chest wall. Dose calculations were performed with Anisotropic Analytical Algorithm version
15.6.05. The FFF plans were then optimized until comparable for PTV coverage to the
previously treated plan.
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 12 patients, the standard deviation,
mean dose, and variance was obtained for FFF and FF plans.
Statistical Analysis
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Each plan was evaluated individually to collect data for this study and compared to
previously approved plans. The one-sided Wilcoxon signed rank tests (WSR) were performed to
compare the distributions for the FFF and FF planning techniques as well as the mean heart dose.
With a family-wise error rate of 5% for the heart, 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 when using FFF compared to FF (P < 0.0005). The mean
heart dose for FFF plans was 1.12 Gy and 1.25 Gy for the FF plans (Table 1). The mean heart
dose comparison between the 2 plans is depicted in Figure 1 and indicated the reduction in mean
heart dose across the population tested for FFF plans. 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, therefore the null hypothesis (H10) failed to be
rejected.
Discussion
The results of the current analysis demonstrated that using 6FFF beams would reduce
mean heart dose; similar to the Barsky et al12 study in which 6FFF was used to reduce heart
toxicity. In the current study, each plan met MROQC and institutional dose volume histogram
(DVH) constraints for target coverage and OAR sparing for all plans. Research has shown that
treatments that utilized DIBH were useful in displacing the heart to decrease the
dose.5,6,7Conventionally, FFF beams have not been used in 3D planning due to the insufficient
ability to deliver homogenous dose to targets.8 However, researchers in the current comparison
study found that FFF produced similar maximum dose distribution within the chest wall in each
plan (Figure 2) and improved mean heart dose without compromising target coverage.
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Radiation therapy for left sided breast cancer leads to an increase risk of significant
cardiac toxicities. In early trials including breast RT, an increase in the number of cardiac deaths
was observed with occurrences higher in left sided versus right sided breast cancer patients than
in right sided disease.4 Darby et al3 showed that for every increase (Gy) in the mean dose to the
heart is increased, the risk for ischemic heart disease increased by 7.4%.3 By using the FFF
technique, it allowed for a sharper dose fall off, which reduced dose to surrounding OAR. Other
trends noticed in this research were heart maximum decreased by 8.4% and left lung maximum
dose was decreased by 0.3%, 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.
In addition to the reduction in heart dose, FFF treatments are significantly faster to treat
than traditional FF treatments. Faster treatment times have the benefit of reducing the likelihood
of patient movement during treatment. Planned monitor units (MUs) per fraction were
significantly higher in the FFF plans compared to the FF plans by approximately 50%. Dose rate
in FFF plan were set at 1400 MU/min and 600 MU/min for FF which leads the FFF plan to be
2.3 times higher. As a result, the treatment delivery was shortened. Takakura et al13 saw similar
results when they compared 6 MV FF and FFF beams using an IMRT technique for cervix
cancer and discovered that FFF irradiation has the advantage of faster treatment to normal tissues
with fewer doses.13
Conclusion
The use of DIBH has proven to be beneficial in displacing the heart and decreasing the
cardiac dose. However, the problem of increased heart toxicity remains for left sided chest wall
patients. The FFF FIF technique has the potential to minimize heart dose for left sided chest wall
patients. Therefore, the purpose of this study was to compare the heart dose for FFF and FF
DIBH FIF treatments for left sided chest wall patients. Researchers in the current study
demonstrated a significant correlation between using the FFF DIBH technique and lower mean
heart dose. Furthermore, results demonstrated that the use of FFF beams provides faster
treatment delivery with less dose to surrounding normal tissues.
The limitations of this study included data collection at a single institution using 1 TPS
and calculation algorithm. Utilizing multiple institutions could provide a more extensive range of
results and population to help validate this study. Additionally, this research could be completed
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using different TPS algorithms or linear accelerators for the same anatomical site to see if similar
results would be presented. Future researchers could evaluate different OAR on the left side of
the patient such as lung dose or the left anterior descending artery, due to the significance in this
study.

Acknowledgements
The authors would like to acknowledge Kelly Kovach and Jean Moran for review of plans and
clinical guidance throughout the study. We would also like to acknowledge Dr. David Reineke
and the Statistics Department at the University of Wisconsin - La Crosse for providing analysis
and interpretation of the statistical data; however, any errors of fact or interpretation remain the
sole responsibility of the authors.
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References
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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
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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.
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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. Tamilarasu S, Saminathan M, Sharma SK, Pahuja A, Dewan A. Comparative Evaluation of a
6MV Flattened Beam and a Flattening Filter Free Beam for Carcinoma of Cervix – IMRT
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Planning Study. Asian Pac J Cancer Prev. 2018;19(3):639-643. Published 2018 Mar 27.
doi:10.22034/APJCP.2018.19.3.639
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
12. 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.
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Figures

Figure 1. Boxplot of the reduction in heart mean dose showing how much lower the dose is
using flattening filter free (FFF) than with flattening filter (FF) DIBH FIF treatments for left-
sided chest wall patients. The differences along with a reference line at 0 for comparison are
shown above.

Figure 2. Axial comparison between flattening filter free (FFF) on the left and flattening filter
(FF) on the right. The 2 Gy isodose line in blue visually shows less volume in the heart for FFF
compared to FF beam.
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Tables

Table 1. Standard deviation, sample size, mean, and variance for 6FFF and 6FF mean heart dose.
Data Parameters 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
FFF= flattening filter free; FF= flattening filter