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Evaluation of DIBH breast plan robustness against isocenter positioning uncertainties

Cory Tuzzo, BS, R.T.(T); Carli Doerr, BS, R.T.(T); Benjamin Smith, BS, R.T.(T)
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI
Introduction
Left breast radiation treatment objectives include adequate target coverage while
minimizing doses to organs at risk (OAR) such as the heart. Due to differences in patient
anatomy and laterality, heart dose can vary significantly. A previous study by Darby et al1
revealed patients who received left breast radiation treatment had a 25% increased risk of late
cardiac toxicity. Furthermore, cardiac mortality for left-sided breast cancer patients has shown to
be significantly higher than right-sided.2 Therefore, it is crucial to assess every aspect of left
breast treatment planning to ensure the patient safety by reducing these possible complications
from radiation exposure to the heart while maintaining target coverage.
Deep inspiration breath hold (DIBH) treatment is a patient breathing technique monitored
by surface tracking (AlignRT) to decrease the risk of increased heart dose. Reducing radiation
dose to the heart through a treatment and planning technique such as DIBH is a viable option for
many left breast cancer patients.3 Deep inspiration breath hold treatment works by allowing the
lungs to be completely full of air, shifting the treatment volume anteriorly and laterally away
from the heart.4 There are 2 types of DIBH with 1 involving an active breathing coordinator in
which the patient is coached to breathe through a specified mouthpiece when instructed.5 The
other type of DIBH is completely done voluntarily by the patient where a breath is held for a set
amount of time.6 There are different approaches to reaching the optimal patient setup with DIBH
thresholds. AlignRT, the surface image tracking system, provides real-time, non-invasive
monitoring of the patient’s surface anatomical position to help reduce uncertainties during the
DIBH treatment.7 While AlignRT is not able to remove treatment uncertainty entirely, this
technology remains a frontrunner for DIBH treatments.
Uncertainties can arise from various error sources, all of which can affect the planned
dose distribution. Errors such as patient positioning inaccuracies, changes of the breast tissue,
and patient movement all have a factor in a patient’s treatment delivery.8 When radiation
therapists align the patient for treatment, there are often slight positioning inaccuracies. During
the course of radiation therapy, the patient’s treated breast may experience edema which is a side
effect from the radiation. The difference in breast tissue size can cause a discrepancy with the
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planned dose distribution. As for patient movement during the radiation therapy treatment, DIBH
may be utilized to help control one aspect of this particular uncertainty when the radiation is
being delivered. With the patient in the fixed breath hold position, the motion of the treated
volume is more controlled during irradiation. However, this does not account for the uncertainty
of patient movement during the entire treatment process. Even though DIBH is designed to
reduce the patient movement uncertainty of the affected breast that can alter the planned dose
distribution, it cannot account for all uncertainties including errors in patient positioning or
patient movement throughout the treatment.
To improve the level of uncertainty that occurs with patient positioning and movement,
AlignRT incorporated threshold tolerances that are set for all linear translations (vertical, lateral,
longitudinal, roll, pitch, and yaw). These tolerances notify the radiation staff if the patient is
positioned or moves outside of the set limitations. Depending on the facility, the threshold
tolerance may be 2 mm, 3 mm, or 4 mm. Due to the fact that patients have the tendency to move
throughout treatment which is directly proportional to the amount of time on the table, these
tolerances are in place to account for this variable motion.9 Wiant et al9 discuss how patients
monitored with surface imaging, such as AlignRT, may benefit from smaller threshold
tolerances. However, with the knowledge that DIBH increases the amount of time the patient is
on the table, the tolerances need to reflect this as well.9 It is this balance between surface imaging
and length of treatment that threshold tolerances average around 3 mm between departments.
Even though these threshold tolerances account for small patient positioning errors and patient
movement, the patients planned dose distribution may be inaccurate should the tolerances be
implemented on a daily basis.
A new tool, known as plan uncertainty, was applied in the Eclipse treatment planning
system (TPS) version 13 that can help assess the robustness of plans with simulated isocenter
shifts. When this tool is applied to a plan, Eclipse will generate and calculate dose distributions
of several model plans according to the arbitrary shifts of isocenter defined by the user.10 These
simulated isocenter shifts represent the various errors (mentioned above) that create uncertainties
within the treatment plan and help to decipher whether the threshold tolerances in AlignRT need
to be adjusted to keep the dose distribution within the plan’s dose constraints.
The research problem is that patient positioning errors could be shifting the isocenter
resulting in an unplanned increase in cardiac dose and decreased evaluation planning target
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volume (PTV Eval) dose coverage for left-sided breast patients treated with DIBH. The overall
purpose of this study is to compare heart dose and Breast PTV Eval coverage for DIBH left
breast patient plans using the plan uncertainty feature in Eclipse to determine whether
adjustments are necessary for threshold tolerances. Incorporating isocenter shifts of 3 mm in the
X, Y, and Z directions using the uncertainty tool, researchers tested the following hypotheses:
(H1A) meet all criteria for breast PTV and heart dose goals for less than 100% of patients, (H2A)
show > 10% of the entire heart receiving > 22 Gy with an isocenter shift within the department
setup margins, (H3A) show mean heart dose receiving > 2.5 Gy with an isocenter shift within the
department setup margins, (H4A) show 90% of the Breast PTV Eval receiving < 90% of the
prescription dose with an isocenter shift within the department setup margins, (H5A) show
unacceptable dose constraints with > 35% of the Breast PTV Eval receiving > 100% of the boost
prescribed dose of 39.6 Gy with an isocenter shift within the department setup margins, (H6A)
show > 50% of the Breast PTV Eval receiving > 38.3 Gy with an isocenter shift within
department setup margins.
Methods and Materials
Patient Selection and Setup
Nineteen patients were selected for this retrospective study. The inclusion criteria were
that each patient was diagnosed with early stage left breast cancer. All patients were treated for
whole left breast cancer using the voluntary deep inspiration breath hold (DIBH) technique. The
exclusion criteria were unqualified candidates for the DIBH technique.
All patients were simulated on a Siemens Somatom Confidence CT scanner using a slice
thickness of 2 mm. For the simulation and treatments, patients were positioned supine, head-first,
with both arms above the head, head turned away from the affected side, and the knees slightly
bent over a foam cushion. The immobilization device used was an alpha cradle to keep the upper
bodies in a reproducible position.
Contours
The structures contoured for each patient followed the protocol of their enrolled clinical
trial, the NOVEMBER Trial (more information about the trial is discussed later). The organs at
risk included the lungs, contralateral breast, heart, ribs, and thyroid. The lungs were contoured
using the auto-segmentation with manual verification. The contralateral breast and heart contours
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followed the Radiation Therapy Oncology Group (RTOG) Breast Atlas and RTOG 1106
contouring guidelines, respectively. The ribs and thyroid structures were contoured manually.11
The volumes that were drawn by the physicians included the following lumpectomy and
breast volumes for the treated left breast: Lumpectomy Gross Tumor Volume (GTV), separate
Lumpectomy and Breast Clinical Target Volumes (CTV), separate Lumpectomy and Breast
Planning Target Volumes (PTV), and separate Lumpectomy and Breast PTV Eval structures.
The PTV Eval structures were the PTVs but excluding the part outside the ipsilateral breast, the
first 5 mm of tissue under the skin (in order to remove most of the buildup region for the dose
volume histogram [DVH] analysis), and any expansion that extends beyond the posterior extent
of breast tissue. The PTV Evals were the structures used for DVH constraints and analysis.11
For the purpose of this study, only the heart and Breast PTV Eval structures were used
for evaluation. The other structures were still contoured but not used for evaluation in collecting
data. All structures contoured were reviewed and approved by the attending physician.
Planning Procedures
All of the patients were planned in the Eclipse treatment planning system (TPS) version
15.5, and the dose was calculated with the Acuros External Beam algorithm version 15.5. The
plans were all optimized with Radformation EZFluence software to eliminate any bias during
plan evaluation. Plans were created for a Varian Clinac iX Linear Accelerator using portal
imaging as well as AlignRT for surface guidance monitoring to confirm patient positioning. Each
patient in this study followed the NOVEMBER Protocol. This protocol is a hypofractionation
trial to improve overall cosmetic results, convenience and cost effectiveness while still delivering
the equivalent cancer control.11 Each patient was prescribed a 9-day course of whole breast
radiotherapy. The breast was prescribed 3.8 Gy for 9 fractions totaling 34.2 Gy with a
lumpectomy boost prescribed to 0.6 Gy for 9 fractions totaling 5.4 Gy. For this study, the Breast
PTV Eval total dose will be evaluated based on the contribution from the whole breast
radiotherapy as well as lumpectomy boost. All plans had the same dose constraints following the
NOVEMBER Protocol.11
In this study, the plan uncertainty tool was used to simulate patient setup errors with an
isocenter shift of 3 mm. The 3 mm metric is a standard AlignRT tolerance in the department
where the patients were planned and treated. Seven plans were calculated for each patient: the
original plan and the 6 plans generated following a simulated isocentric shift of ±3 mm along the
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axis in all directions (X, Y, and Z). All 7 calculated plans were compared in a DVH to evaluate
the original plan’s robustness (Figure 1). For all 19 patients in this study, a total of 133 plans
were calculated for evaluation.
Statistical Analysis
By definition, the P-value in a hypothesis test is the probability of observing at least as
much evidence against the null hypotheses as what is currently observed, given that the null
hypothesis is true. Since each null hypothesis states that 100% of patients in the intended
population will satisfy a specific criterion, then when the null hypothesis is true, it will be
impossible to observe any patients in any sample that will not satisfy the criteria. If none of the
patients in the sample fail to meet the criterion, the P-value will be 1, since all possible samples
will contain only patients that satisfy the criterion when the null hypothesis is true. If one or
more of the patients in the sample fails to meet the criterion, the P-value must be 0, since this
would be impossible when the null hypothesis is true. The research hypothesis (H1A) looks at all
five dosimetric constraints of this protocol as a whole while H2A to H6A hypotheses examine
each individual constraint.

Results
Overall Dose Criteria
The hypotheses tests are based on the basic and defining characteristics of statistical
inference. Seventeen of the 19 left breast patients passed all 5 dose criteria. Two patients did not
meet at least one of the dose criteria. Both instances occurred in examining the Breast PTV Eval
(Table 1). Researchers rejected the null hypothesis (H10) at α = 0.05. There is sufficient evidence
to conclude that incorporating isocenter shifts within the departmental setup margins of 3mm in
the X, Y, and Z directions using the uncertainty tool will meet all criteria for breast PTV and
heart dose goals with an isocenter shift within the department setup margins for < 100% of
patients (P=0)
Dose to 10% of Heart
All 19 patients in this sample met the dose constraint of 10% of the entire heart receiving
< 22 Gy. Researchers failed to reject the null hypothesis (H20) at α = 0.05. There is insufficient
evidence to conclude that incorporating isocenter shifts within the departmental setup margins of
3 mm in the X, Y, and Z directions using the uncertainty tool will show > 10% of the entire heart
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receiving 22 Gy with an isocenter shift within the department setup margins for < 100% of
patients (P = 1.0).
Mean Heart Dose
All 19 patients in this sample met the dose constraint of mean heart dose < 2.5 Gy.
Researchers failed to reject the null hypothesis (H30) at α = 0.05. There is insufficient evidence
to conclude that incorporating isocenter shifts of 3 mm in the X, Y, and Z directions using the
uncertainty tool will show the mean heart dose receiving 2.5 Gy with an isocenter shift within
the department setup margins for < 100% of patients (P = 1.0).
90% Breast PTV Eval
All 19 patients in this sample met the dose constraint of 90% of the Breast PTV Eval
receiving at least 90% of the prescription dose. Researchers failed to reject the null hypothesis
(H40) at α = 0.05. There is insufficient evidence to conclude that incorporating isocenter shifts of
3 mm in the X, Y, and Z directions using the uncertainty tool will show the mean heart dose
receiving > 2.5 Gy with an isocenter shift within the department setup margins for less than
100% of patients (P = 1.0).
Breast PTV Eval Boost Dose
One patient in this sample failed the dose constraint of < 35% of Breast PTV Eval
receiving 100% of the prescribed boost dose of 39.6 Gy. The researchers rejected the null
hypothesis (H50) at α = 0.05. There is sufficient evidence to conclude that incorporating isocenter
shifts of 3 mm in the X, Y, and Z directions using the uncertainty tool will show 35% of the
Breast PTV Eval receiving 100% of the boost prescribed dose of 39.6 Gy with an isocenter shift
within department setup margins for < 100% of patients (P = 0).
50% of Breast PTV Eval Dose
One patient in this sample failed the dose constraint of >50% of the Breast PTV Eval
receiving 38.3 Gy. The researchers rejected the null hypothesis (H60) at α = 0.05. There is
sufficient evidence to conclude that incorporating isocenter shifts of 3 mm in the X, Y, and Z
directions using the uncertainty tool will show >50% of the Breast PTV Eval receiving 38.3 Gy
with an isocenter shift within department setup margins for 100% of patients (P = 0).
Discussion
The results of this study showed that incorporating isocenter shifts of 3 mm in the X, Y,
and Z directions using the uncertainty tool will show that less than 100% of patients will meet all
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five dose criteria. Researchers rejected 3 of the 6 null hypotheses (H10, H50 and H60) and 17 of
the 19 patients failed to meet all of the dose criteria. The 3 mm setup margins are based on the
AlignRT surface imaging system as well as length of treatment. A study by Wiant et al9
demonstrated that longer treatment times result in an increased chance of random patient
movement. Setup margins should account for this type of uncertainty as well as internal organ
variance on a daily basis.
The results show that the threshold tolerances that are currently in place for this sample
are indeed sufficient for most patients. With 17 of the 19 meeting all the dose constraints, the
threshold tolerance of 3 mm should continue to be the starting point. However, with 2 patients
not meeting all dose constraints, this data should not be overlooked. Radiation Oncologists and
Medical Physicists should review each patient individually to determine if tighter setup margins
are needed for that specific patient. Utilizing the uncertainty tool in Eclipse TPS for every DIBH
left breast patient prior to treatment in order to determine that specific patient’s threshold
tolerance is the recommendation from these results.
Conclusion
The purpose of this study was to compare heart dose and Breast PTV Eval coverage for
DIBH left breast patient plans using the plan uncertainty feature in Eclipse to determine whether
adjustments are necessary for set up threshold tolerances. Utilizing the plan uncertainty tool
showed that 89.5% of our patient sample met all dose criteria. The combination of DIBH and
surface image tracking help to limit dose to the heart while still adequately treating the left
breast.
Limitations of this study included all patient treatment plan data were collected from one
cancer center, with one TPS and calculation algorithm. Results could vary slightly from a
different linear accelerator causing more patients to fail specific dose criteria. Future research
could include a larger sample size and patient data from multiple cancer centers. Furthermore,
different threshold tolerances could be used. A 3 mm margin was sufficient for a breast tangent
treatment, however, a different margin could be evaluated as well as a different anatomical site.
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Updated May 8, 2020. Accessed July 23, 2020.