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A comparative study of cone beam CT organs at risk shifts in breast radiotherapy: free
breathing vs. deep inspiration breath hold scan sequences

Ryann Edwards, BS; Milica Ilic, BS, RT(R); Nishele Lenards, PhD, CMD, RT(R)(T), FAAMD;
Ashley Hunzeker, MS, CMD, Ashley Cetnar, PhD, DABR

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

Introduction
Breast radiotherapy aids in the local control and survival rate for breast cancer patients,
but there is concern over cardiac toxicity relating to radiation therapy.1 The heart is one of the
major organs at risk (OAR) for breast radiotherapy, especially in the case of left side-breast
radiotherapy due to the location of the heart being slightly to the left of midline within the chest
cavity. Radiation exposure to the heart is the most well-known risk factors for developing
coronary artery disease and cardiac mortality.1,2 The risk of heart disease and coronary events is
estimated to increase 4-7% for every 1 Gy in mean heart dose.1,3 Saini et al4 showed that there
was a 50% relative reduction in the mean heart left anterior descending artery dose between free
breathing (FB) and breath hold (BH) plans. In addition to the heart, it is essential to assess the
lungs as additional crucial OAR during breast radiation therapy. Heart and lung mean doses
drastically decrease by up to 60% using abdominal and thoracic breath hold methods.5
Maintaining a consistent focus on restricting patient movement ensures that patients stay
still and receive the correct prescribed dose in the intended area of their body during treatment. 5
Respiration should be closely monitored and evaluated in all imaging specialties. Radiotherapy
treatment advancements have included the use of deep inspiration breath hold (DIBH) techniques
as an aid in regulating patient breathing and as a tool to improve OAR sparing during treatment
planning.1 During a CT simulation scan for breast radiotherapy are several techniques to manage
motion. This includes using immobilization techniques such as using Alpha cradles and Vak-
Loks. Respiratory management techniques that are often used in radiotherapy include DIBH. 1
Deep inspiration breath hold is a technique in which the patient takes a deep breath and then
holds it for a period during the CT simulation. This technique is based on the observation that
during inspiration, the diaphragm flattens, the lungs expand, and the heart is retracted from the
chest wall.1,6 Utilizing the DIBH technique increases distance from the chest wall and provides a
more optimal physical location for treating the affected breast tissue while limiting dose to OAR.
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Deep inspiration breath hold techniques include 2 different commonly used methods
which are voluntary DIBH (vDIBH) and moderate DIBH.1 Patients that undergo vDIBH are
instructed to hold their breath at certain points in the breathing cycle. Depending on the type of
equipment available, this often includes gating patient respirations by placing a device on the
patient’s chest or abdomen to measure vertical displacement. The greater the vertical
displacement of the chest or abdomen could signify a greater difference in internal motion.
Treatment is withheld when the patient is not at a desirable lung capacity. 1 Moderate DIBH
includes coupling patients to Active Breathing Coordinator (ABC) devices to allow for
monitoring of airflow and ensure that patients remain at a desired breath hold volume.1 An ABC
device utilizing the moderate DIBH method incorporates a spirometer-based valve system to
monitor airflow and lung volume of the patient on a screen provided both in the room for the
patient and for therapists outside of the treatment room.7 Physicians will often order both an FB
and BH CT simulation for evaluation prior to beginning the treatment planning process due to
the possible benefits patients may receive by using a DIBH method.
While deep inspiration breath hold techniques provide benefits to patient treatment, not
all patients can undergo the process of DIBH without complications or overexertion. Due to
these possibilities, it is standard at most clinics to have both scans completed for treatment
planning evaluation. If the physician finds there to be no considerable reduction in dose to OAR
using the DIBH scan, the FB scan will be used. Additionally, if the patient faced difficulties and
overexertion with the ABC devices, the FB simulation scan will be used. Oonsori et al8 suggested
that the patient is likely to feel an immense amount of pressure during the BH simulation scan,
which deteriorates the success of the DIBH technique. The session can take around 20-30
minutes, which can make the patients uncomfortable and increase their stress and anxiety as a
result.8 Kron and Bressel et al9 found that the mean anxiety score for 30 breast cancer patients
performing a DIBH for CT simulation was 4.3 out of 10, with 13% of them feeling ‘quite a bit’
or ‘very much’ worried they would not hold their breath correctly. The sensitivity to an
individual’s respiratory rate can be directly affected by various factors and stressors, especially
emotional stressors.10 Recognizing and skillfully addressing emotional stressors can significantly
boost the overall success and comfort of patients during their cancer treatment. It is crucial to
acknowledge that a patient's emotional state directly influences the quality of simulation scans. If
a patient has not reached a state of complete ease with the procedure, there is a possibility that
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their anxiety or stress could manifest in the resulting simulation scans. Thus, patients need to be
properly coached in the process of the DIBH CT scan and allowed time to adapt to the clinical
setting. Without the proper preparation and training prior to obtaining simulation scans, the
patient will not be in the same physical and emotional state they will be on the first day of
treatment. Radiation therapists and physicians can review patient anatomy by evaluating a cone
beam CT (CBCT) scan on the first day of treatment. These CBCT scans are used to track patient
anatomy and positioning to ensure little to no variation is present. However, proper coaching and
preparation are crucial for DIBH scans due to potential patient anxiety and stress.
Protocols for the sequence of FB and DIBH simulation scans may vary among clinical
sites and are often based on physician preference. One concern is that the FB scan may not
accurately represent the patient's true free breathing conditions, as it may show residual anxiety
impacts from emotional stressors and overexertion caused by the prior DIBH scan. This can
become problematic when the physician elects to use the FB scan over the BH scan for treatment
planning. To address this issue of possible OAR misalignment and ensure proper patient
positioning, OAR are delineated on the FB simulation scan used for planning. Delineation of the
OAR aids in proper alignment at the time of CBCT acquisition. However, challenges arise when
comparing the delineated OAR with the OAR on CBCT scans taken on the first day of treatment
and there is misalignment of OAR. The misalignment between the FB simulation and CBCT
scans can affect the accuracy of patient positioning and tracking patient progression, potentially
leading to treatment discrepancies. Therefore, establishing consistent protocols for the sequence
of simulation scans and refining the alignment process between FB and CBCT scans is crucial
for enhancing the precision and effectiveness of radiation therapy treatments. The problem is that
the delineated OAR from the FB simulation scans do not line up accurately to the CBCT scans
on the first day of treatment.
Therefore, the purpose of this retrospective study is to compare FB and DIBH CT
simulation scans and evaluate OAR shifts to determine if the cause of the shifted CBCT
OAR on first day of treatment is due to the sequence of the scans. Researchers tested
hypotheses that there will be a reduction of ≥10% in shifts to the lungs (H1A) and heart
(H2A) when the sequence of simulation scans was altered to FB followed by DIBH.

Methods and Materials

Patient Selection and Simulation Setup
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A total of 18 patients who received breast radiotherapy from a single institution were
selected for this retrospective study. Population size was limited due to the number of patients
who had also received a CBCT for positioning verification. The inclusion criteria were patients
treated for breast cancer with a specific order of CT simulation scans. Patients included were
those who had a FB CBCT verification on the first day of treatment and treatments whose were
planned on the FB simulation scan. Group 1 consisted of patients who were simulated DIBH
first, followed by a FB scan. Group 2 consisted of patients who were simulated for a FB
simulation scan first, followed by a DIBH scan second. The selection of these groups was to
evaluate if the order of the simulation scans completed affects how well delineated OAR from
the planning CT align to the CBCT OAR. It is important to note that the clinical site that the
pertinent data was collected from did not have established protocols on the sequence of scans
completed. Of the 18 patients, 9 had FB scan prior to DIBH scan and the 9 had DIBH scan prior
to FB scan. Treatment techniques used for planning were not considered. Affected breast side
with disease was not considered as the study encompassed both left and right sided patients.
However, most patients included in the study were left sided cases.
Each patient underwent a DIBH CT simulation and a FB CT simulation. For positioning
reproducibility, patients were simulated supine with their arms raised and immobilized in an
Alpha Cradle for both the DIBH CT and FB. For the DIBH CT each of the patients were
simulated with the Elekta ABC device to monitor their breathing patterns and ensure patients
withheld a constant air volume threshold (Figure 1). A Phillips Big Bore CT scanner was used to
acquire the planning CTs with 3.0 mm slice thickness. The anatomy included on the simulation
scans began superiorly at the level of the mandible and extended inferiorly through the
diaphragm.

Image Registration
Prior to treatment delivery, radiation therapists performed a CBCT scan for patient
alignment of the treatment area to the planning FB CT. The CBCT scans from day 1 of treatment
were fused registered to the treatment planning FB scan to evaluate the location of the heart and
the affected ipsilateral lung utilizing Medical Imaging Management (MIM). A rigid based fusion
was completed for every patient with the CBCT from day 1 of treatment and FB treatment
planning scan. The MIM software application was utilized for the alignment of the CW for all
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patient registrations. The chest wall was referenced during registration due to limited changes in
anatomy.
Contours
Following fusions of the scans, the heart and the lungs were contoured on all CBCT
scans. The heart and lungs were contoured following the guidelines suggested by the Radiation
Therapy Oncology Group (RTOG) 1005 and RTOG 1106 protocols for breast and thoracic
irradiation.11 The heart contour begins inferior to the bifurcation of the pulmonary artery. The
mediastinal heart tissue following this bifurcation was included on every slice inferiorly leading
to the diaphragm and along the pericardium. The affected ipsilateral lung was contoured using an
auto segmentation feature with manual verification using lung window levels. This included the
apex of the lung superiorly and to the base of the lung inferiorly.
Evaluation
Evaluation of anatomy shifts utilized both the coronal plane and the transverse plane. The
coronal plane was referenced to obtain shift measurements for the lungs. Measurements for the
lung were taken at a point midplane and at mid-depth of the lung for all patient scans. Shifts for
the lung were measured at the most inferior aspect near the bases as this is where lung motion
and movement are most affected due to the diaphragm and liver employing the measuring tool
available in MIM. For right-side affected patients, the liver dome was used as a reference and for
left-sided patients the diaphragm was used as point reference. The transverse plane was used to
obtain measurements for the heart. The points of measurement for the heart were recorded at a
point midplane and mid-depth for all patients. The shift measurement was taken from the edge of
the delineated OAR on the planning CT to the corresponding edge of the delineated OAR on the
CBCT. The mean shift in centimeters (cm) for each group for the heart and lungs was calculated
and used for statistical analyses.
Statistical Analysis
The OAR shift measurements were reviewed to determine the appropriate method for
statistical analysis. Shapiro-Wilk tests were used to determine the normality of the differences in
each group. Both data sets for the heart and lungs in each group were analyzed. The Shapiro-
Wilk test deemed the data sets to be normally distributed. A two-sample t-test was performed for
all metrics to determine if the difference in means between both groups was statistically
significant. Following the recorded data sets' evaluation, a one-tailed test was used because of the
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decrease in shifts presented between groups. Due to a small sample size, a significant p value of
P < 0.1 was utilized to find a significance more adequately in the data set.

Results
Lung Mean Shifts
The mean lung shift for Group 1 was 1.62 cm with a standard deviation of 0.86 cm and
the mean lung shift for Group 2 was 0.51 cm and a standard deviation of 0.27 cm (Figure 2). The
amount of shift present in the lungs for Group 1 ranged from 0.61 cm to 2.68 cm. In comparison,
the amount of shift present in Group 2 ranged from 0.22 cm to 1.05 cm. Upon evaluation of the t-
test, a statistically significant difference between the 2 groups was observed (P= 0.001). Upon
evaluating the mean lung shifts of both groups, there is a 68.7% reduction of shifts seen between
Group 1 and Group 2. Therefore, researchers rejected the null hypothesis (H10) and witnessed a
decrease in lung shifts > 10%.
Heart Mean Shifts
The mean heart shift for Group 1 was 0.91 cm and a standard deviation of 0.43 cm. The
mean heart shift for Group 2 was 0.37 cm with a standard deviation of 0.14 cm (Figure 3). The
amount of shift present in the heart for Group 1 ranged from 0.38 cm to 1.73 cm. In comparison,
the amount of shift present in Group 2 ranged from 0.22 cm to 0.67 cm. Upon evaluation of the t-
test, a clinically significant difference between the 2 groups was observed (P= 0.001). Upon
evaluating the mean heart shifts of both groups, there is a 64.7% reduction of shifts seen between
Group 1 and Group 2. Therefore, researchers rejected the null hypothesis (H20) and witnessed a
decrease in heart shifts > 10%.
Discussion
Upon evaluation of lung mean shifts, it is evident that Group 2, where FB scans preceded
DIBH scans, demonstrated a statistically significant reduction in mean lung shifts compared to
Group 1, which initiated with DIBH scans. The mean lung shift presented by Group 1 was 1.62
cm with a standard deviation of 0.86 cm. The mean lung shifts presented by Group 2 was 0.51
cm with a standard deviation of 0.27 cm. The significance of this finding is underscored by the
notable 68.5% reduction in lung shifts witnessed in Group 2, presenting with a decrease in shifts
>10%. The implications of these results underscore the relevance of commencing the simulation
process with FB scans to potentially enhance lung positioning stability and, by extension, the
accuracy of radiation therapy delivery, while mitigating undue radiation exposure to healthy lung
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tissue. These results emphasize the importance of carefully considering the sequence of
simulation scans in breast radiotherapy planning. Beginning with FB scans may allow patients to
acclimate to the clinical setting, reducing anxiety and stress, which could contribute to more
stable lung positioning and a natural respiratory rate that would be later observed at the time of
treatment delivery. Moreover, this reduction in lung shifts has the potential to enhance the
precision of radiation therapy delivery and decrease the risk of irradiating healthy lung tissue.
The evaluation of heart mean shifts similarly revealed a statistically significant difference
between Group 1 and Group 2. Group 1 exhibited a mean heart shift of 0.91 cm, with a standard
deviation of 0.43 cm, while Group 2 showed a mean heart shift of 0.37 cm, with a standard
deviation of 0.14 cm. This represents a notable 59.3% reduction in heart shifts in Group 2,
demonstrating a reduction of shifts >10%. Reducing heart shifts is of paramount importance in
breast radiotherapy, as excess radiation exposure to the heart is a well-known risk factor for
coronary artery disease and cardiac mortality.4 These results suggest that initiating the simulation
process with FB scans may contribute to more favorable heart positioning, potentially
minimizing the risk of cardiac toxicity and improving patient outcomes.
The findings presented have important clinical implications for breast radiotherapy
planning. Establishing a standardized protocol favoring FB scans followed by DIBH scans may
be considered to reduce OAR shifts, particularly in lung and heart positioning. This
recommendation assumes heightened significance, particularly concerning pulmonary
positioning, as evidenced by a more pronounced reduction in shifts observed within lung data
points in comparison to those affecting cardiac data points. Such a protocol could help maintain
patient comfort, alleviate anxiety, and improve the accuracy of radiation therapy treatment.
Establishing a protocol for the sequence of simulation scans completed will also aid in creating a
more reproducible and identical patient set up for treatment. In circumstances where physicians
elect for planning on the FB scan that was completed first, there will be no residual effects from
a DIBH scan. Completing the DIBH scan will likely have no residual effects from a FB scan
completed prior, as shown by the data of this study. Furthermore, addressing patient anxiety and
stress during the simulation process is essential. The study highlighted that patients may
experience discomfort and anxiety during DIBH scans, potentially compromising the quality of
imaging. Thus, it is imperative to provide comprehensive patient preparation, coaching, and
support to enhance their comfort and cooperation during the procedure. This approach may
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involve addressing emotional stressors and allowing sufficient time for patients to adapt to the
clinical environment. Thus, in patient cases where a DIBH scan is completed first, with proper
coaching and preparation shifts in OAR could potentially be limited further. During this time for
preparation is the time for a physician to determine which technique would best benefit the
patient. Every tumor is unique just as every patient is unique. The use of a DIBH method may
not be the most beneficial option for a patient. Other patients may benefit more from the use of
other gating devices such as abdominal or thoracic devices or without any devices on a FB scan.
This retrospective study establishes that altering the sequence of FB and DIBH
simulation scans yields significant influences on OAR shifts, notably reducing lung and heart
shifts when commencing with FB scans. These findings advocate for the adoption of a
standardized protocol that favors FB scans followed by a DIBH, if the physician requests one.
Patient comfort and emotional well-being during the simulation process must be evaluated prior
to beginning the simulation process. For a patient to benefit the most amount possible from their
radiotherapy treatments, simulation set ups must be easily reproducible. This should include the
emotional as well as the physical wellbeing of the patient. Ultimately, these considerations have
the potential to enhance the precision and efficacy of breast radiotherapy treatments, minimizing
the chances of dosimetric error.
Conclusion
The problem is that the delineated OAR from the FB simulation scans do not line up accurately
to the CBCT scans on the first day of treatment. The purpose of this retrospective study is to
compare FB and DIBH CT simulation scans and evaluate OAR shifts to determine if the
potential cause of the shifted CBCT OAR on the first day of treatment is due to the sequence of
the scans. Altering the sequence of FB and DIBH simulation scans yields a significant influence
on OAR shifts. When the FB scan preceded the DIBH scan, there was a 68.5% reduction in lung
shifts and a 59.3% reduction in heart shifts. The findings indicate that a standard protocol should
be implemented, one in which FB scans should be performed prior to DIBH scans.
The limitations of this study included a limited population size (n=18) at a single institution.
Including a larger number of patients from multiple institutions could reduce the effects of
outliers during statistical analysis. The study was also limited due to CBCT scans being partial
scans. Future research could include obtaining full CBCT scans to also include the liver for
further OAR analysis. Incorporating full CBCT scans also allows for the opportunity to
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accurately determine trace lung volumes between the FB treatment simulation scan and the
CBCT scan completed on the first day of treatment. Future research can also incorporate
volumetric shifts based on point locations for more accuracy.
Acknowledgements
The authors would like to thank Dr. Douglas Baumann of the Statistical Consulting
Center at the University of Wisconsin - La Crosse for assistance with analysis and interpretation
of statistical data; however, any errors of fact or interpretation remain the sole responsibility of
the authors.
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Figures

Figure 1. Elekta ABC device (courtesy of and with permission from Elekta).

Figure 2. Box-whisker plot of measured lung shifts (cm) for Group 1 and Group 2.
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Figure 3. Box-whisker plot of measured heart shifts (cm) for Group 1 and Group 2.