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Research Proposal (Quantitative)

Title: Evaluation of DIBH breast plan robustness against isocenter positioning uncertainties
Literature Review Summary (Introduction)
Left breast radiation treatment objectives include adequate target coverage while
minimizing doses to organs at risk (OAR) such as the heart. Certain breast treatment plans can
result in higher heart doses due to different patient anatomy. A previous study by Darby et al1
revealed patients who received left breast radiation treatment had a 25% increased risk of late
cardiac toxicity. Preston et al2 showed survivors of the atomic bombings of Hiroshima and
Nagasaki had a 17% increased risk of death from heart disease due to radiation. Therefore, it is
crucial to assess every aspect of breast treatment plans to ensure the safety of the patients by
reducing these possible complications from exposure to the heart. Deep inspiration breath hold
(DIBH) is a planning and treatment technique used to mitigate cardiac toxicity by reducing dose
to the heart, proving to be a viable option for many left breast cancer patients.3
Deep inspiration breath hold treatment is a patient breathing technique monitored by
surface image tracking (AlignRT), to decrease the risk of increased heart dose. Deep inspiration
breath hold treatment works by allowing the lungs to be completely full of air, depressing the
heart posteriorly and medially out of the radiation field.4 There are two types of DIBH with 1
involving an active breathing coordinator (ABC_DIBH) in which the patient is coached to
breathe through a specified mouthpiece when instructed. The other type of DIBH is completely
done voluntarily (V_DIBH) by the patient where a breath is held for a set amount of time.5 There
are different approaches to reaching the optimal patient setup with DIBH thresholds. As
previously mentioned, AlignRT is a surface tracking system that offers real-time, non-invasive
monitoring of the patient’s surface anatomical position and remains a frontrunner for DIBH
treatments.6 This real-time monitoring helps to reduce uncertainties within the treatment.
These 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, or patient movement all have a factor in a patient’s treatment delivery.7 A new tool,
known as “plan uncertainty,” was implemented in version 13 of the Eclipse treatment planning
system (TPS) 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. The problem is that
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patient positioning errors could be shifting the isocenter resulting in an unplanned increase in
cardiac dose and decreased evaluation planning target volume (PTV Eval) dose coverage for left-
sided breast patients treated with DIBH. The 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 set up threshold tolerances.
Problem Statement
The problem is that patient positioning errors could be shifting the isocenter resulting in an
unplanned increase in cardiac dose and decreased evaluation planning target volume (PTV Eval)
dose coverage for left-sided breast patients treated with DIBH.
Purpose Statement
The 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 set up threshold tolerances.
Hypothesis
The research hypothesis (H1) is that using the uncertainty tool will show > 10% of the whole
heart receiving ≥ 22Gy with an isocenter shift within the department setup margins. The null
hypothesis (H10) is that using the uncertainty tool will not show > 10% of the whole heart
receiving ≥ 22Gy with an isocenter shift within the department setup margins. The 2nd research
hypothesis (H2) is that that using the uncertainty tool will show the mean heart dose receiving >
2.5 Gy with an isocenter shift within the department setup margins. The 2nd null hypothesis (H20)
is that using the uncertainty tool will not show the mean heart dose > 2.5Gy with an isocenter
shift within the department setup margins. The 3rd research hypothesis (H3) is that using the
uncertainty tool will show 90% of the Breast PTV Eval receiving < 90% of the prescription dose
with an isocenter shift within departmental setup margins. The 3rd null hypothesis (H30) is that
using the uncertainty tool will not show 90% of the Breast PTV Eval receiving < 90% of the
prescription dose with an isocenter shift within department setup margins. The 4th research
hypothesis (H4) is that using the uncertainty tool will show unacceptable dose constraints with >
35% of the breast PTV Eval receiving > 100% of the boost prescribed dose of 39.6Gy with an
isocenter shift within department setup margins. The 4th null hypothesis (H40) is that using the
uncertainty tool will not show > 35% of the breast PTV Eval receiving >100% of the boost
prescribed dose of 39.6Gy with an isocenter shift within department setup margins. The 5th
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research hypothesis (H5) is that using the uncertainty tool will show > 50% of the breast PTV
Eval receiving > 38.3Gy with an isocenter shift within department setup margins. The 5th null
hypothesis (H50) is that using the uncertainty tool will not show >50% of the breast PTV Eval
receiving >38.3Gy with an isocenter shift within department setup margins.

Methods and Materials

Patient Selection
Nineteen patients were selected for this retrospective study. Each patient was diagnosed
with early stage breast cancer and is undergoing the November Protocol Clinical Trial. This
November Protocol is a hypofractionation trial to improve overall cosmetic results, convenience
and cost effectiveness while still delivering the equivalent cancer control.8 These patients were
treated for whole left breast cancer using the DIBH technique. They were all treated head-first,
supine with an alpha cradle for immobilization.
Planning Procedures
All of the patients were planned in the Eclipse TPS version 15.5, and the dose was
calculated with the Acuros External Beam algorithm version 15.5. The plans were optimized
with the help of Radformation’s EZFluence software. EZFluence is an automated 3D planning
software that generates optimal fluence and simplifies field-in-field planning while maintaining
or improving plan quality compared to manual techniques.9 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. For the November Protocol, each patient was
prescribed a 9 day course of whole breast radiotherapy. The breast was prescribed 380cGy for 9
fractions totaling 3420cGy with a lumpectomy boost prescribed to 60cGy for 9 fractions totaling
540cGy. When applying EZFluence to the treatment planning process, the boosts become
simultaneously integrated in the plans. All plans had the same dose constraints following the
November Protocol. The critical structures contoured that will be included in this study are the
volumes for the treated breast and heart. Heart contours followed the Radiation Therapy
Oncology Group (RTOG) 1106 guidelines. The breast contour follows RTOG breast atlas
guidelines.
The ‘plan uncertainty’ tool will be applied to each plan with the parameters set for patient
setup with an isocenter shift of 0.3cm. Seven plans will be calculated for each patient: The
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original plan as well as the six plans that will be generated following a simulated isocentric shift
of 3mm along the axis in all directions (±X, ±Y, and ±Z).
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References

1. Darby S, 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):987–98.
http://dx.doi.org/10.1056/NEJMoa1209825
2. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of atomic
bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950–1997. Radiat
Res. 2003;160:381–407. http://dx.doi.org/10.1667/rr3049
3. Conroy L, Yeung R, Watt E, et al. Evaluation of target and cardiac position during visually
monitored deep inspiration breath-hold for breast radiotherapy. J Appl Clin Med Phys.
2016;17(4):25-36. http://dx.doi.org/10.1120/jacmp.v17i4.6188
4. Hayden A, Rains M, Tiver K. Deep inspiration breath hold technique reduces heart dose
from radiotherapy for left sided breast cancer. J Med Imaging Radiat Oncol. 2012;56:464–
72. http://dx.doi.org/10.1111/j.1754-9485.2012.02405
5. Bartlett F, Colgan R, Carr K, et al. The UK HeartSpare Study: Randomised evaluation of
voluntary deep inspiratory breathhold in women undergoing breast radiotherapy. Radiother
Oncol. 2013;108:242–7. http://dx.doi.org/10.1016/j.radonc.2013.04.021
6. Xiao A, Crosby J, Malin M, et al. Single-institution report of setup margins of voluntary
deep-inspiration breath-hold (DIBH) whole breast radiotherapy implemented with real-time
surface imaging. J Appl Clin Med Phys. 2018;19(4):205-213.
http://dx.doi.org/10.1002/acm2.12368
7. Mourik AV, Kranen SV, Hollander SD, Sonke J-J, Herk MV, Vliet-Vroegindeweij CV.
Effects of Setup Errors and Shape Changes on Breast Radiotherapy. Int J Radiat Oncol Biol
Phys. 2011;79(5):1557-1564. http://dx.doi.org/10.1016/j.ijrobp.2010.07.032
8. Poppe M, Kokeny K, Gaffney D, Burton L, Cannon D, Kim J. NOVEMBER (Novem- (9),
BrEast Radiation), A Phase II trial of a 9 day course of whole breast radiotherapy for early
stage breast cancer. Huntsman Cancer Institute. Salt Lake City, Utah. Version date: August
16, 2019.
9. Sysock K. EZFluence. Radformation. https://www.radformation.com/ezfluence/ezfluence.
Accessed April 7, 2020.