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A retrospective study of left-sided breast patients to determine optimal lung and cardiac-
sparing treatment position.
Nathaniel Miles, Maddisen Fain, Mary Keating R.T.(T)., Ashley Hunzeker, M.S.,
CMD, Nishele Lenards, M.S., CMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI

ABSTRACT
The goal of this retrospective study was to evaluate if a tool or metric can be developed that
predicts optimal cardiac and lung sparing without the need for patients to undergo multiple CT
scans. Thirty-five females diagnosed with breast cancer contained to the left breast were
simulated in 3 different positions: supine free-breathing (FB), supine deep inspiration breath-
hold (DIBH), and prone. Treatment plans prescribed to 45 Gy in 28 fractions were created in
each position utilizing the Eclipse treatment planning system (TPS). Tangential treatment
field border parameters were set as outlined in the Radiation Therapy Oncology Group (RTOG)
breast atlas. The heart and ipsilateral lung were contoured as per the RTOG 1106 thoracic
atlas and the mean and maximum were compared between each simulation position. Patient
factors including BMI, smoking status, breast size and primary tumor quadrant were
evaluated. P-value tests were performed to evaluate the change in mean heart and lung
doses. Scatter plots were created to evaluate for correlation between sternal separation and the
change in mean heart and lung doses from FB to DIBH scans. Although this study failed to
develop a tool or metric that is predictive of optimal cardiac and lung sparing positioning, each
patient should be at a minimum simulated in the prone or DIBH position to ensure a reduction in
the mean heart dose.
Introduction
The American Cancer Society estimates greater than 266,000 new cases of breast cancer will
be diagnosed in the United States in 2018.The 5-year survival rate is 99% for patients with
disease in only one breast without nodal involvement.1 Since most individuals diagnosed with
early stage breast cancer will be cured of the disease, survivorship is an important topic. A recent
review suggested that radiation therapy (RT) should be recommended for 87% of breast cancer
patients.2 The main long-term hazards of breast cancer irradiation are that it may cause a second
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primary cancer in the lung or cardiac complications.3 Minimizing dose to the heart and lung is of
vital importance to increase the chance of a morbidity-free survival.
The increasing survival rate for breast cancer patients has prompted a growing concern to
reduce the risk of developing a secondary lung malignancy or cardiac complication.4,5 Grantzau
et al5 evaluated the effects of breast cancer radiation to the risk of developing a second primary
lung cancer and found an 8.5% linear increase per Gy. In left breast RT treatments, the heart can
receive increased exposure to ionizing radiation due to its location when compared to right-sided
tumors. Increased exposure can increase the subsequent rate of ischemic heart disease, which has
been found to be proportional to the mean heart dose. The rates of major coronary events
increase linearly with the mean heart dose by 7.4% per Gy.6 A recent international breast cancer
randomized trial (NSABP B-51/RTOG1304) proposed the mean heart dose (Dmean Heart) should
be less than 4 Gy during left-sided breast/chest wall irradiation. 7 DIBH and prone positioning
RT planning techniques are currently recommended by the National Comprehensive Cancer
Network (NCCN) to reduce heart and lung dose.8 Several studies have been performed that
acknowledge the benefit of utilizing different positioning and treatment techniques to reduce
cardiac dose. 2-4,6-7,9-15,17-20,23-26 Yet, there are a lack of guidelines as to the best practice in cardiac
sparing.9 The widespread availability of prone breast boards and surface-guided RT systems
have enabled radiation oncology departments to perform multi-positional CT
simulations. However, no tool or metric has been published that allows for evaluation of best
scenario heart and lung sparing in left-sided breast patients without having to obtain CT scans in
numerous treatment positions.
Lara et al10 reported that there has not been a thorough comparison of the mean dose to the
heart for all breast techniques, for various breast sizes and/or seroma locations. So Lara et al
compared mean heart doses for a left breast irradiated with different techniques. However, the
evaluation utilized an anthropomorphic Rando phantom rather than actual patients.
Bouchardy et al11 investigated 1245 node-negative breast cancer patients that were irradiated
between 1980 to 2004 and died of cardiovascular disease. The study assessed tumor location and
found that patients with inner-quadrant tumors had a more than doubled risk of cardiovascular
mortality compared with patients with outer-quadrant tumors; the risk increased for those who
had boost irradiation. One limitation of this study was that all the patients were treated in the
supine position.
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Zhao et al4 showed that DIBH can achieve lower ipsilateral lung and cardiac doses compared
to FB plans. DIBH causes an increased spatial separation between the heart and target volume,
which results in a decreased volume of the heart within the tangential fields.12 In DIBH
respiration, the distance of chest wall movement can be increased up to about 12.6 mm. 13
Lowanichkiattikul et al14 evaluated factors affecting chest wall movement during various phases
of respiration and found that the chest wall moved less in the anterior-posterior (AP) direction
for obese patients than in those with a with a normal BMI. Lung vital capacity has also been
shown to strongly correlate with the chest wall movement .15 However, smoking can decrease
chest wall expansion, forced vital capacity, and maximal expiratory muscle strength.16 Yet, a
systematic review of the cardiac dose-sparing benefits of DIBH did not show any study that
evaluated BMI or compared smokers to non-smokers.12
Walston et al17 evaluated the dosimetric sparing of organs using the DIBH technique versus
FB and sought to find a correlation between the chest wall excursion from the couch top and
benefits in heart and lung sparing. Although Waltson et al failed to find a correlation, they
revealed a dosimetric advantage could be better achieved by measuring heart to tangential field
border. Nissen and Appelt18 also evaluated FB versus DIBH techniques and found there to be a
lack of predicting factors determining whether a patient will benefit substantially from
DIBH. For individual patients it is difficult to predict the optimal treatment position without
taking both FB and DIBH CT scans into consideration.
Lymberis et al19 evaluation of prone versus supine positions found that although prone
treatment is generally reserved for women with large, pendulous breasts, the prone setup reduced
the amount of irradiated lung in all patients. The study found that for left breast cancer patients,
the prone position was always superior in women with breast volumes >1500 cc, in 95% of
women with breast volumes of 750 to 1500 cc, and in 68% of women with breast volumes of
<750 cc. The study also found prone positioning to reduce the amount of heart volume irradiated
in 87% of left breast patients. However, it did not compare the prone to DIBH position. Chen et
al20 evaluated 25 women by measuring the heart to tangent field border looking for correlation to
cardiac dose reduction but it also only compared heart-sparing in the prone versus supine
positions.
The existing literature showcased the need for the current study to be conducted. This
study compared patients in 3 positions to evaluate if a tool or metric can be developed that
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predicts optimal cardiac and lung sparing without the need for patients to undergo multiple CT
scans. Individuals diagnosed with early stage left-sided breast cancer have a high rate of success
for cure. Therefore, it is imperative that dosimetric measures be taken to ensure that their
survivorship is not burdened by preventable co-morbidities. Additionally, in adherence with the
radiation principle of “as low as reasonably achievable” (ALARA), radiation oncology
professionals should strive to find a guideline for a best practice in lung and cardiac sparing. The
goal of this retrospective study was to develop a tool that predetermines best position for optimal
heart and lung sparing to minimize multiple CT scans.
Methods and Materials

Patient Selection
Thirty five patients selected for this study were diagnosed with cancer of the left breast
without lymph node involvement. Each patient underwent CT simulations in the prone, supine
FB, and supine DIBH positions. The simulations were performed in 1 of 4 centers within a multi-
site network. In all simulations, the field borders were delineated with wire. The scan length
included the entirety of the ipsilateral lung with the superior border at the level of the chin and
the inferior border 5 cm below the visible breast tissue.
During simulation, each patient underwent a FB and DIBH CT scan on a MedTec breast
board with the arms overhead (Figure 1). A Vacloc bag was positioned under the torso for
immobilization purposes. The tumor bed scar, field borders, nipple, and central axis (CAX) were
delineated with radio opaque wire or markers (Figure 2). The chin was turned to the
contralateral side and raised slightly. Once properly immobilized, the patient underwent both FB
and DIBH CT scans using either a GE Lightspeed or a Philips Brilliance Big Bore CT scanner
with 2.5 mm axial slice thickness. First, the FB scan was performed. The breath hold was timed
for 20 seconds at which the patient was then directed to breathe. This was repeated at least once
to ensure the patient was comfortable with the process and duration of the breath hold prior to
the scan. Upon demonstration of appropriate breath hold technique the patient was scanned
holding their breath.
Following completion of the FB and DIBH simulations, the patient was simulated in the
prone position on a CDR prone breast board. The radiation therapist indexed the prone breast
board to ensure that the hole for breast placement was large enough to keep the field borders
from touching the breast board whenever possible. The midline marker was kept 1-2cm from the
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breast board whenever possible. Care was taken to ensure no skin folds existed between midline
and the contralateral breast and inferior breast tissue and abdomen. The head was turned in the
direction that the patient found most comfortable. The borders from supine position were used. A
radio opaque marker designating the prone position CAX was placed on the outer-laterality,
midway between the superior and inferior borders, of the left breast (Figure 3). The patient was
then scanned in the prone position. Each scan was then sent to Raystation TPS.
Contouring
The patient DICOM data sets were anonymized and sent to 2 centers for contouring. Contouring
was performed on each of the prone, DIBH, and FB using either Raystation or Eclipse TPS. The
contours included the heart, ipsilateral lung, and the radio opaque markers which indicated the
location of the nipple and each of the field borders drawn by the physician at the time of CT
simulation (Figure 4). The physician designated field borders to comply with the RTOG Breast
Atlas. The superior field border was placed at the level of the second rib insertion; the caudal
border was placed inferior to the inframammary fold using clinical judgment to delineate the
termination of breast tissue. The lateral border was placed at the mid axillary line, excluding the
latissimus dorsi. Lastly the medial border was placed midline at the level of the sternal rib
junction.21
The heart and left lung were contoured referencing the RTOG 1106 Thoracic Atlas. The
lungs were contoured using pulmonary windows. All inflated and collapsed, fibrotic and
emphysemic lung tissue was contoured; the small vessels extending beyond the hilar region were
included. The hila and trachea were not included in the lung tissue contour. The heart and
pericardial sac were contoured. The superior aspect of the heart began at the level of the inferior
aspect of the pulmonary artery passing the midline and extended inferiorly to the apex.22
Treatment Planning
Tangential fields were created utilizing the borders indicated by the radiation oncologist
at the time of simulation. The medial radio opaque marker was used as a user origin/localization
point for all scans. The same isocenter shift was used for the FB and DIBH CT scans as the
medial marker was not moved between scans. The DIBH shift was found first by placing the
isocenter in the center of the breast. The prone isocenter was placed in the center of the breast.
The gantry was rotated until the medial and lateral markers were in alignment. The collimator
was rotated to follow the chest wall. A rectangular field was created using the field border
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defining markers placed at the time of CT simulation and 2cm of flash was created anteriorly
(Figure 5). Medial and lateral tangents were created, and field divergence was matched along
posterior border.
All plans were calculated to receive 45 Gy in 25 fractions at 180 cGy per day. The plans
were calculated using 6 MV energy if the posterior field border on the localization slice was less
than 24 cm from medial to lateral. If the border was larger than 24 cm, 18 MV was used. The
DIBH plan was normalized first by placing a calculation point in the same axial plane as the
isocenter 1 cm from the chest wall halfway between the medial and lateral borders of the
posterior field edge. The DIBH plan was then normalized to this point. All other plans used the
same normalization values as the DIBH plan. All plans were calculated for the same Varian
TrueBeam linear accelerator using Eclipse TPS and Analytical Anisotropic Algorithm (AAA).
To reduce variation between the plans, none were weighted, no blocks were drawn, no field-in-
fields were used, and no wedges were added. The plans were kept as open fields with equal beam
weighting.
Once the fields were created and dose was calculated, both the mean and maximum doses
for the heart and lung were measured for all patients in each of the 3 positions. Additionally, the
hotspot was recorded for each plan. A sternal separation measurement was obtained for the
DIBH by measuring the difference in distance from couch top to skin between DIBH and FB
(Figure 6). A heart separation from tangential field to pericardium between DIBH and FB was
also obtained (Figure 7). The breast size was recorded as well and was determined by measuring
from the medial to lateral field edge at the level of isocenter (Figure 8).
Plan Comparisons
The mean and maximum heart and lung doses were averaged for each of the FB, DIBH,
and prone positions. P-value tests were performed to evaluate the change in mean heart and lung
doses. P-values of ≤ 0.05 were considered statistically significant. The mean heart and lung
doses with each technique were then compared to several different patient measurements to
evaluate for correlation. The mean heart and lung dose were compared to the breast size, breast
quadrant, smoking status and BMI.
A scatter plot was created to determine if there was a correlation between heart separation
and the change in mean heart dose from FB to DIBH scans. A comparison between heart
separation and the change in lung/heart dose from FB to DIBH scans was also made using a
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scatter plot. Additional scatter plots were created to evaluate for correlation between sternal
separation and the change in mean heart and lung doses from FB to DIBH scans.
A table of demographic information and the change in mean lung and heart dose
associated with the different groups was created to see if specific techniques were superior based
on demographics. Some of the demographics evaluated included whether a patient was a current
or former smoker, whether a patient was considered obese from their BMI, a patient's breast size
(less or greater than 24cm), and the seroma location within the breast quadrant.
Results
The study included 35 females with left sided breast cancer. Table 1 represents the
clinical characterization of the patients involved in the study. As shown, the patients' age ranged
from 30 to 75 years with a median of 58 years. The median BMI was 28.7. Only 1 woman was a
current smoker, 16 women were former smokers, and 18 have never smoked. Most patients were
diagnosed with a type of ductal carcinoma, with 34.3% having ductal carcinoma in situ (DCIS)
and 48.6% having invasive ductal carcinoma (IDC). Only 2.8% of patients had lobular
carcinoma (LCIS) and 14.3% were diagnosed with invasive lobular carcinoma (ILC). Primary
tumor location included the following: 45.7% of all tumors were found in the upper outer
quadrant (UOQ), 17.1% were located in the upper inner quadrant (UIQ), 14.3% were located in
the lower outer quadrant (LOQ) and 22.9% in the lower inner quadrant (LIQ). Only 2.8% of
patients had a triple negative immunohistochemistry (IHC) expression of estrogen receptor (ER),
progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). 42.8% of
patients were ER/PR+, Her2- and 14.2% were ER/PR+, Her2+. The DCIS and LCIS patients
were not tested for Her2, but all were found to be ER/PR+. Only 5.6% of patients were found to
be ER/PR- (Table 1).
The average mean and maximum heart dose were found to be higher in the FB plan than
in DIBH or the prone plans (Table 2). The average mean heart dose was 182cGy for the FB plan
versus 132cGy for the DIBH plan and 120cGy for the prone plan. The average maximum heart
dose was 2798cGy for the FB plan versus 1523cGy for the DIBH plan and 1739cGy for the
prone plan. The mean and maximum lung doses were highest in the DIBH plans with a mean
lung dose of 524cGy and the maximum lung dose was 3858cGy. The average mean DIBH lung
dose was 0.8% higher than the FB plan and10.6% higher than the prone plan. The average
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maximum DIBH lung dose is 2.6% higher than the FB plan and 58.1% higher than the prone
plan.
P-value tests were performed to evaluate the change in mean heart and lung doses
(Tables 3-4). The change in mean heart dose between positions was found to be statistically
significant for the FB versus DIBH and prone positions. There was no statistical significance
between the prone and DIBH positions. There was also a statistical significance in the change of
mean lung dose for the prone position as compared to both the FB and DIBH positions. The
statistics show that overall DIBH was better for mean and maximum heart dose with an average
of 2.93% and 33.84% of prescription, respectively, as compared to 4.04% and 62.17% for the FB
scans. Prone proved be the best option dosimetrically for virtually all the patients, with
improvements in mean and maximum heart and lung dose in comparison to both the FB and
DIBH scans.
The dose statistics between the factors that we assessed, such as breast size, sternal
separation, smoking status, and breast quadrant failed to show any correlation (Table 5). The
heart separation versus FB-DIBH mean heart dose did show some correlation when the heart
separation measured was over 1.5cm (Figure 9-12). This showed that patients with this large
amount of heart separation, at least in the plane measured, had the greatest benefit from a DIBH
treatment plan. Patients with less heart separation only averaged around 1% mean heart dose
sparing while patients over 1.5cm of separation showed increasing benefit, with the patient who
had a heart separation of around 2.5cm of separation receiving the most benefit of over 5%
improvement.
Discussion
This study failed to find correlation between any measurements that would be predictive
of the best position for the treatment of left-sided breast cancer patients. The patients' smoking
status, BMI, primary tumor quadrant, and breast size were not predictive of mean heart or lung
dose. Single slice data obtained at the level of isocenter including sternal separation, heart
separation, and breast size were also not predictive of a guideline for optimal positioning
practice.
A multi-institutional study of greater than 10-year survivors of breast cancer noted that
smoking and RT together increased the risk of fatal myocardial infarction (MI).23 Unfortunately,
in the current study, patient smoking status was not indicative of the mean heart or lung dose.
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The smoking status did not correlate to the sternal or heart separation. A measurement of lung
volume might have correlated better to sternal or heart separation. Due to the increased risk of
MI, left-sided breast cancer patients who maintain a current smoker status should be offered
simulations in each position to determine which is most advantageous.
It is known that the DIBH technique reduces the mean heart dose through
immobilization of the chest wall and by increasing the distance from the heart.12,24 However,
sternal separation measured at the level of isocenter did not prove to be a good indicator of
improvement between the DIBH and FB positions. This could simply be attributed to the fact
that patients breathe differently, with some breathing more from their diaphragm and others
breathing more with their whole chest.4,25 Furthermore, in the prone position where sternal
separation was negligible, the mean heart dose was found to be lower than that of both FB and
DIBH plans.
The measurement of heart separation at the level of isocenter did not show correlation to
the mean heart or lung dose. This might be attributed to the position of the heart at the level of
isocenter. Greater separation might be seen at another level of the heart such as the apex and a
distance measurement could potentially prove to be statistically significant. Additionally, the
heart moves with the respiratory cycle so the degree of motion, mainly in the superior–inferior
direction, is modest with free breathing.26 An ECG may be a way to minimize radiation exposure
and determine the proximity of the heart to the chest wall in various treatment positions.
Breast size measured on a single slice and BMI showed no correlation to each other.
They also were not predictive of heart and lung doses. However, Brown et al27 has shown that
BMI and suprasternal notch to nipple distance enable predictions of breast mass. A measurement
of breast mass such as this may show correlation to lung and heart dose.
Finally, although primary tumor breast quadrant statistics did not correlate to lung or
heart dose in this study, the patients in this study did not have a boost prescribed. As indicated in
Bouchardy et al11, the quadrant location may be predictive of positional benefits when a tumor
bed boost is prescribed. Positioning patient based on the cavity might reduce the heart and lung
from additional exposure as it relates to the boost.
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Conclusion
In conclusion, this study failed to find correlation between any measurements that would
be predictive of the best position for the treatment of left sided breast cancer patients and
minimize the number of CT simulations. Breast size, breast quadrant, smoking status, and BMI
did not prove to be measures that correlate to the best treatment position. However, because the
prone and DIBH position showed a significant decrease in the mean heart dose as compared to
the FB scans, patients should be offered treatment in one of these positions if they are able to
tolerate it.
One possible limitation of this study was the limited sample size used. This retrospective
analysis included only 1 current smoker. If a larger number of patients with a current smoking
habit were included in the study then a correlation between heart and lung dose may have been
discovered. The more comprehensive data could then be used to evaluate treatment positions.
Another limitation of this study was the evaluation of measurements taken in a single
plane. The heart separation may have been a more meaningful statistic if measurements were
made in each plane and these statistics were averaged. The volume and relative movement of
heart determined by an ECG may be more predictive of which treatment position would most
likely reduce cardiac dose. Evaluation of breast mass might have proven a more useful statistic
than the single measurement of medial to lateral border at the level of isocenter.
Centers should continue to perform CT simulations in each of the DIBH, FB, and prone
positions to ensure that each patient has the best opportunity for the creation of an individualized
treatment plan which best minimizes heart and lung dose during the treatment of left-sided breast
cancer.
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Figures

Figure 1. Patient setup lying supine on the breast board from MedTec with the arms positioned
overhead.

Figure 2. Patient markings in the supine position.


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Figure 3. Patient setup lying prone on the breast board from CDR with the CAX indicated by the
mid-breast marker.

Figure 4. Radio opaque markers (red) placed on the nipple and at the level of the field borders
drawn at the time of CT simulation.
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Figure 5. Tangential field creation and collimator rotation set by following the chest wall.

Figure 6. The sternal separation measured on both the DIBH (left) and FB (right) CT data sets.
17

Figure 7. The heart separation measured on both the DIBH (left) and FB (right) CT data sets.

Figure 8. The breast size measurement as determined by measuring from the medial to lateral
field edge at the level of isocenter.
18

Figure 9. A comparison between heart separation and the change in mean heart dose from FB to
DIBH scans. 
19

Figure 10. A comparison between heart separation and the change in mean lung dose from DIBH
to FB scans. 
20

Figure 11. A comparison between sternal separation and the change in mean heart dose from FB
to DIBH scans. 
21

Figure 12. A comparison between sternal separation and the change in mean lung
dose from DIBH to FB scans. 
22

Tables

Table 1. The clinical characterization of patients.

Parameter Total
Age (Years) Min-Max 30-75
Median 58
Weight (Lbs.) Min-Max 115-246
Median 173
Height (in.) Min-Max 156-69
Median 65
BMI Min-Max 22-42.6
Median 28.7
Smoking Status (%) Non 51.4
Former 45.8
Current 2.8
Tumor Quadrant (%) UOQ 45.7
LOQ 14.3
UIQ 17.1
LIQ 22.9
Diagnosis (%) DCIS 34.3
IDC 48.6
LCIS 2.8
ILC 14.3
IHC Expression (%) ER/PR+,Her2+ 14.2
ER/PR+,Her2- 42.8
ER/PR+,Her2 37.4
unknown 2.8
ER/PR-,Her2+ 2.8
ER/PR-,Her2-

Table 2. Average mean and maximum dose for heart and lung for each scan.

Parameter  FB (%) DIBH (%) Prone (%)


Mean heart  4.04  2.93  2.66 
Max heart  62.17  33.84  38.64 
Mean lung  10.8  11.64  1.08 
Max lung  85.29  87.95  29.88 
23

Table 3.  Statistical significance of change in mean heart dose (n=35)


Parameter  P-Value 
FB versus DIBH  0.001 
FB versus Prone  0.033 
DIBH versus Prone  0.54 

Table 4.  Statistical significance of change in mean lung dose (n=35).

Parameter  P-Value 
FB versus DIBH  0.13 
FB versus Prone  0 
DIBH versus Prone  0 

Table 5. Average change in mean heart dose between scans for patient demographic data.

Parameter  FB-DIBH (%) FB-Prone (%) DIBH-Prone (%)


Non-smoker  1.31  1.75  0.44 
Current smoker   1.1  2.5  1.4 
Former smoker  0.89  0.91  0.01 
BMI >30%  1.06  1.23  1.72 
BMI <30%  1.16  1.54  0.38 
UOQ Quadrant   1.61  2.41  0.79 
LOQ Quadrant   0.32  -0.04  -0.36 
UIQ Quadrant   1.2  1.17  -0.03 
LIQ Quadrant   0.44  0.21  -0.23 
Breast size >24cm  1.04  1.44  0.4 
Breast size <24cm  1.36  1.13  -0.23