1

A comparison of respiratory management techniques using phase gating and end

expiratory breath hold during SBRT to spare healthy liver tissue for patients with liver
metastases
Jaclyn Wanie, BS, RT(T); Jacob Wudtke, BS, RT(T); Margaret Koehn, BS, RT(T); Nishele
Lenards, PhD, CMD, RT(R)(T), FAAMD; Ashley Hunzeker, MS, CMD; Matt Tobler, CMD,
RT(T), FAAMD
Medical Dosimetry Program at the University of Wisconsin-La Crosse, WI
Abstract
Respiratory management techniques have allowed patients to experience less side effects
from liver stereotactic body radiation therapy (SBRT) but is difficult for all patients to perform
correctly. The problem is that sparing healthy liver tissue is difficult due to respiration that
results in liver movement during SBRT treatment. While the use of phase gating (PG) respiratory
management is easier for patients to perform, there is a paucity of literature comparing PG to end
expiration breath hold (EEBH) as a method of respiratory management. The purpose of this
comparison study was to evaluate liver motion during PG and EEBH SBRT treatments and
measure dose to healthy liver by quantifying the cubic centimeters (cm3) of healthy liver
receiving > 15 Gy. Eleven patients with metastatic liver cancer were included, each simulated
using four-dimensional computed tomography (4DCT) for accurate treatment planning. Various
contours and planning structures were generated to assess target coverage and healthy liver
sparing. Two SBRT treatment plans, one for EEBH and another for PG, were developed for each
patient. On average, PG plans exhibited a higher volume of healthy liver receiving > 15 Gy
compared to EEBH plans, and researchers demonstrated statistically significant data that PG has
a significantly higher volume of healthy liver receiving > 15 Gy compared to EEBH. Although
PG is an acceptable technique utilized for maintaining target coverage, its potential for increased
healthy liver exposure to radiation doses exceeding 15 Gy should be considered. In addressing
the challenge of preserving healthy liver tissue during SBRT for liver metastases, researchers
demonstrated that EEBH may offer a more favorable approach compared to PG.
Keywords: SBRT, liver metastases, phased gating, end expiration breath hold, respiratory
management
Introduction
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A distinctive biological trait of malignant tumors is the ability to metastasize or invade

other tissues than the one it originated in.1 Metastatic tumors account for about 90% of deaths due
to cancer and are generally associated with poor prognosis.2 Certain primary cancers tend to
metastasize to specific areas of the body, but in general, the most common areas of metastases
are the brain, bones, lungs, and the liver.2 While the prognosis for patients with metastases at
diagnosis is generally poor, patients who present with only liver metastases have a greater
prognosis than those with metastases to other sites or multiple sites.2 The incidence of liver
metastases is profound; out of 1,630,725 cases of cancer recorded in the Surveillance,
Epidemiology, and End Results Program, 6.46% of cases present with liver metastases at
diagnosis.3 With proper treatment, especially with early intervention, liver metastases can be well
controlled and distant metastases can be prevented.
A common treatment for liver metastases when the lesions cannot be treated with surgery
or ablation therapy due to operational risks, is radiation therapy.3 Specifically, liver metastases
can be treated with stereotactic body radiation therapy (SBRT), which is a method of treating
very small cancerous lesions to a high dose with small planning target volume (PTV) margins.3
Since the targets are often smaller in size, SBRT treatments allow for a greater amount of healthy
tissue surrounding the lesion to be spared, ultimately saving the patient from more significant
side effects. A Phase I trial was conducted in a multi-institutional setting to evaluate the safety of
using conformal SBRT doses to treat liver metastases, which researchers found that using doses
of approximately ≤ 50 Gy in 10 treatments was safe and effective for clinical use.4 This
fractionation scheme is commonly used to treat liver metastases, with great success of tumor
control. However, despite the use of SBRT and small margins, patients still experience side
effects due to radiation treatment.
Common side effects that patients experience after radiation treatment for liver
metastases include fatigue, nausea and vomiting, and other gastrointestinal problems such as
diarrhea.5 A rare and morbid side effect of radiation to the liver is radiation-induced liver disease
(RILD), which can be fatal.5 Patients experience RILD side effects because some amount of
healthy tissue, defined as the total liver volume excluding the gross tumor volume (GTV), is still
irradiated during radiation treatment, even with careful planning. The recent introduction of
respiratory management of breathing control helps to reduce internal patient motion, potentially
aiding in the reduction of these side effects.
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Respiratory management is a tactic used during radiation therapy that restricts internal
motion caused by breathing. Deep inspiration breath hold (DIBH) and end expiration breath hold
(EEBH) are utilized commonly.6,7,8 Both DIBH and EEBH require the patient to hold their breath,
either at the top of their breath cycle or the bottom, respectively.7 Some patients may have trouble
with these techniques, because certain comorbidities such as chronic obstructive pulmonary
disease can make it difficult to achieve the breath holds necessary for treatment. Furthermore,
those who are naturally short of breath may also have difficulty performing a breath hold. Not
only is this uncomfortable for patients, but inadequate breath holding can cause variances in
target position daily. Another option for respiratory management is a respiratory PG window for
treatment.9,10 When this tactic is used, the patient will breathe naturally but the treatment system
will only deliver radiation during a specific window of their breathing cycle, most commonly
between 40% and 60% of their full inspiration.9 All of these motion management methods allow
patients to receive the highest quality of radiation treatment with reduced side effects.
Respiratory management techniques have allowed patients to experience less side effects
from SBRT to the liver but is difficult for all patients to perform correctly. The problem is that
sparing healthy liver tissue is difficult due to respiration that results in liver movement during
SBRT treatment. While the use of PG respiratory management is easier for patients to perform,
there is a paucity of literature comparing PG to EEBH as a method of respiratory management.
The purpose of this comparison study was to evaluate liver motion during PG and EEBH SBRT
treatments and measure dose to healthy liver by quantifying the cubic centimeters (cm 3) of
healthy liver that receives > 15 Gy. Researchers tested hypothesis (HA) utilizing EEBH will lead
to 5% fewer cm3 of healthy liver volume receiving 15 Gy compared to phase gating, while
maintaining Radiation Therapy Oncology Group (RTOG) 0438 guidelines for target coverage
and OAR constraints.4
Materials and Methods
Patient Selection and Setup
Eleven patients who received liver irradiation from a single institution were selected to be
included in this study. Inclusion criteria for those selected for the study were patients who had
metastatic liver cancer and were simulated using four-dimensional computed tomography
(4DCT). Additionally, patients required magnetic resonance imaging (MRI) for accurate GTV
localization.
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Patients underwent a CT simulation using a Siemens Somatom Definition Edge in a

headfirst supine position with their arms above their head. For immobilization and
reproducibility, each patient was simulated with a custom Civco Vac-lok with clear plastic wrap
compression set to 60 pounds per square inch (PSI). Slice thickness for the 4DCT was set to 2.0
mm, and patients were scanned from carina to middle of the femurs. Utilizing the 4DCT allowed
for 2.0 mm slices to be acquired at 20% increments of the patient’s full respiration cycle.
Contouring
After CT simulation was complete, each patient data set was anonymized and exported to
MIM (Version 6.9.6; MIM Software, Cleveland, OH) for contouring. A single radiation
oncologist contoured the GTV on the treatment planning CT. The GTV was localized by fusing
the EEBH CT (expiration on 4DCT) to a diagnostic MRI acquired at expiration. The PTV was
created for the EEBH scan by expanding the GTV by 5.0 mm, creating PTV_5000_EEBH. The
EEBH CT scan was fused with the full breathing cycle of the PG 4DCT and translated
appropriately to ensure anatomical alignment. Once the fusion was successfully completed, the
GTV was transferred from the EEBH scan to the average 4DCT scan. Subsequently, the GTV
was evaluated for motion across the multiple phases of the 4DCT. A gating window of 40% to
60% was selected as the optimal gating range for the PG scan.7 This created an internal target
volume (ITV). To establish the PG PTV (PTV_5000_PG), the ITV was expanded according to
the deviation in motion of the liver from the 40% to 60% scan.7
One researcher contoured all applicable organs at risk (OAR) which included the entire
liver, small bowel, large bowel, stomach, right kidney, left kidney, right lung, and left lung.
Planning risk volumes (PRV) were created for the stomach and right kidney to evaluate the dose
due to potential motion during treatment. For proper data analysis, lateralized structures were
combined into a single bilateral structure (lungs and kidneys). Retrospectively, a planning
volume was created that subtracted the GTV (EEBH plan) and the ITV (PG plan) from the entire
liver so that dose to healthy liver tissue could be evaluated.
Treatment Planning
Planning structures and OAR were imported to RayStation Treatment Planning System
(TPS) (Version 11B, RayStation, Madison, WI). Two SBRT treatment plans were developed for
each patient using a fractionation scheme of 50 Gy in 5 fractions. The plans were generated for
treatment on a Varian TrueBeam STx. Flattening filter free 10 MV (10 FFF) beams were used at
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a dose rate of 2400 cGy/minute, and the leaf width used was 2.5 mm. Volumetric modulated arc
therapy (VMAT) technique was used, creating 2 partial arcs on the patient’s right side. Arcs
rotated from 32° to 185° counterclockwise and 186° to 33° clockwise with collimator angles of
330° and 30°, respectively. Institutional standards required a maximum hot spot value ≤ 140% or
70 Gy. The EEBH plan had the target structure set as PTV_50_EEBH, and the PG plan had the
target structure set as PTV_50_PG.
Adequate PTV coverage was determined to be 100% of the volume receiving 95% of the
dose, which was 47.5 Gy and was achieved when possible. In select instances, the researcher had
to accept lower PTV coverage to meet the priority 1 liver constraint, which are at least 700 cm 3
receiving < 15 Gy and a mean dose ≤ 15 Gy. To maintain a clinically acceptable treatment plan,
the PG target did not receive full coverage because the PTV_5000_PG was larger than the
PTV_5000_EEBH and exceeded priority 1 liver constraints.
Plan Comparison
Dose distribution to PTV and healthy liver were compared between each patient's plans.
Healthy liver spared was defined by at least 700 cm3 of the Liver-GTV volume receiving < 15
Gy for EEBH plans, and Liver-ITV volume receiving < 15 Gy for PG plans. Ratio of healthy
liver receiving < 15 Gy to total liver volume was evaluated between the 2 techniques.
Statistical Analysis
The data from healthy liver spared were analyzed to dictate a suitable statistical analysis
method. Since 2 sample groups (EEBH and PG) were compared on the same variables, a T-Test
was used to determine statistical significance for this study, with a P-value of 0.05. The volume
of healthy liver tissue spared between EEBH and PG protocols was evaluated. The proportion of
healthy liver receiving > 15 Gy was calculated for PG and EEBH.
Results
Researchers compiled the data from the 11 treatment plans created for each PG and
EEBH gating technique. Researchers evaluated the total cm3 of healthy liver as well as the total
cm3 of liver receiving > 15 Gy. Supplementary tables 1 and 2 were utilized for evaluation of the
difference in healthy liver spared between the 2 gating techniques.
The average volume of Liver-ITV in the EEBH plans was 2393.80 cm3, whereas the
average volume of Liver-ITV in the PG plans was 1983.85 cm3 (Table 1). The volume of Liver-
ITV that received > 15 Gy was measured in each plan to compare which respiratory management
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protocol spared more healthy liver. For EEBH Liver-ITV, the volume receiving > 15 Gy ranged
from 104.39 cm3 to 898.28 cm3, with a mean of 459.09 cm3 (Table 2). For PG Liver-ITV, the
volume receiving > 15 Gy ranged from 142.8 cm3 to 1300.1 cm3, with a mean of 547.47 cm3
(Table 2). The mean proportion of EEBH Liver-ITV receiving > 15 Gy was 0.22 cm3, where the
mean proportion of PG Liver-ITV receiving > 15 Gy was 0.28 cm3 (Table 2).
A T-test was then performed to determine whether PG or EEBH had a greater effect on
healthy liver sparing. The T-test value was 4.306, and the P-value was 0.0007, which exhibited
statistically significant data (Figure 1). A Shapiro-Wilk test was then performed to ensure normal
distribution throughout the data, with the P-value being 0.0527. The results were statistically
significant in that PG had a significantly higher volume of healthy liver receiving > 15 Gy
compared to EEBH; therefore, researchers rejected the null hypothesis (H0).
Discussion
The objective of this study was to spare healthy liver tissue, defined as the volume of
Liver-ITV receiving < 15 Gy. The analysis revealed that EEBH plans had a mean volume of
459.09 cm3 of Liver-ITV receiving > 15 Gy, while PG plans had a mean volume of 547.47 cm3.
Additionally, the average liver-ITV receiving >15 Gy of patients 1 to 11 was 0.22 cm3 for EEBH
and 0.28 cm3 for PG. These results indicated that, on average, PG resulted in a higher volume of
healthy liver receiving > 15 Gy compared to EEBH. Both techniques-maintained target coverage
within acceptable clinical limits according to RTOG 0438, with at least 95% of the PTV
receiving 47.5 Gy in the EEBH and PG plans (Table 1). Target coverage was important to
consider during treatment planning to increase the rates of local control.6,11
The study results have important clinical implications. Healthy tissue sparing is a top
priority for patients undergoing liver SBRT because toxicities like RILD is a possible
complication.6 While both EEBH and PG followed RTOG 0438 protocol, PG appeared to be less
effective in sparing healthy liver tissue. For some patients, EEBH may not be an option due to
other comorbidities making it difficult for some patients to hold their breath. Although
researchers in this study found that EEBH demonstrates less healthy liver being irradiated, it is
important to mention that PG is still an acceptable technique to minimize healthy liver dose.
Understanding that both EEBH and PG are acceptable techniques is particularly relevant
for patients undergoing SBRT for liver metastases. Minimizing radiation-induced damage to the
healthy liver is crucial for reducing treatment-related side effects and improving patient
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outcomes. The researchers also introduced the idea that other treatment sites could benefit from
different gating techniques such as SBRT treatments to the lung or abdomen where breathing
motion may cause intrafraction motion.7
Conclusion
Respiratory management techniques have allowed patients to experience less side effects
from liver SBRT, but is difficult for all patients to perform correctly. The problem is that sparing
healthy liver tissue is difficult due to respiration that results in liver movement during SBRT
treatment. While the use of PG respiratory management is easier for patients to perform, there is
a paucity of literature comparing PG to EEBH as a method of respiratory management. The
purpose of this comparison study was to evaluate liver motion during PG and EEBH SBRT
treatments and measure dose to healthy liver by quantifying the cubic centimeters (cm 3) of
healthy liver receiving > 15 Gy. Researchers tested the hypotheses that utilizing EEBH will lead
to 5% fewer cm3 of healthy liver volume receiving 15 Gy compared to phase gating, while
maintaining RTOG 0438 guidelines for target coverage and OAR constraints.4 The results
indicated that PG was associated with a statistically significant increase in the volume of healthy
liver tissue exposed to doses > 15 Gy compared to EEBH. This outcome suggests that, for
patients undergoing SBRT for liver metastases with a paramount focus on safeguarding healthy
liver tissue, EEBH may offer a more favorable approach.
A limitation of the study included restriction of patients to a single institution. Future
research endeavors should aim to broaden the scope by encompassing patients from diverse
institutions, facilitating a robust validation of these findings. Further investigations can delve
deeper into understanding the influence of respiratory management techniques on liver sparing in
SBRT, potentially leading to enhanced treatment strategies and improved patient outcomes.
Acknowledgements
The authors would like to acknowledge Dr. Douglas Baumann from the University of
Wisconsin – La Crosse Statistics Center for contributing to the statistical analysis portion of the
study. However, any inaccuracies in the statistics or data interpretation are the sole responsibility
of the authors.
References
1. NCI Dictionary of Cancer terms. National Cancer Institute. Accessed June 25, 2023.
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/metastasis.
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2. Wang S, Feng Y, Swinnen J, Oyen R, Li Y, Ni Y. Incidence and prognosis of liver metastasis

at diagnosis: a pan-cancer population-based study. Am J Cancer Res. 2020;10(5):1477-1517.
3. Radiation Therapy for Liver Cancer. American Cancer Society. Accessed June 26, 2023.
www.cancer.org/cancer/types/liver-cancer/treating/radiation-therapy.html.
4. Dawson LA, Winter KA, Katz AW, et al. NRG Oncology/RTOG 0438: A Phase 1 Trial of
Highly Conformal Radiation Therapy for Liver Metastases. Pract Radiat Oncol.
2019;9(4):e386-e393. https://doi.org/10.1016/j.prro.2019.02.013
5. Radiation Therapy Side Effects. National Cancer Institute. Accessed June 26, 2023.
www.cancer.gov/about-cancer/treatment/types/radiation-therapy/side-effects.
6. Gargett M, Haddad C, Kneebone A, Booth JT, Hardcastle N. Clinical impact of removing
respiratory motion during liver SABR. Radiat Oncol. 2019;14(1): 93.
https://doi.org/10.1186/s13014-019-1300-6
7. Oh SA, Yea JW, Kim SK, Park JW. Optimal gating window for respiratory-gated
radiotherapy with real-time position management and respiration guiding system for liver
cancer treatment. Sci Rep. 2019;9(1): 4384. https://doi.org/10.1038/s41598-019-40858-2
8. Sasaki M, Ikushima H, Sakuragawa K, Yokoishi M, Tsuzuki A, Sugimoto W. Determination
of reproducibility of end-exhaled breath-holding in stereotactic body radiation therapy. J
Radiat Res. 2020;61(6):977-984. https://doi.org/10.1093/jrr/rraa079
9. Zeng C, Li X, Lu W, et al. Accuracy and efficiency of respiratory gating comparable to deep
inspiration breath hold for pancreatic cancer treatment. J Appl Clin Med Phys.
2021;22(1):218-225. https://doi.org/10.1002/acm2.13137
10. Eelco L, Gurney-Champion O, Tekelenburg D, et al. Abdominal organ motion during
inhalation and exhalation breath-holds: pancreatic motion at different lung volumes
compared. Radiother oncol. 2016;121(2):268-275.
https://doi.org/10.1016/j.radonc.2016.09.012
11. Pan CH, Shiau AC, Li KC, Hsu SH, Liang JA. The irregular breathing effect on target
volume and coverage for lung stereotactic body radiotherapy. J Appl Clin Med Phys.
2019;20(7):109-120. https://doi.org/10.1002/acm2.12663
Figures
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Figure 1. T-test displaying statistical difference of PG and EEBH healthy liver sparing.
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Tables
Table 1. Comparison of EEBH and PG liver sparing volume
Patient EEBH EEBH EEBH PTV PG Liver- PG Liver- PG PTV
Number Liver-GTV Liver-GTV Coverage GTV GTV Coverage
Volume Volume > (%) Volume Volume > (%)
(cm3) 15 Gy (cm3) 15Gy (cm3)
(cm3)
1 1658.44 180.36 98.87 1590.10 382.60 98.50
2 949.46 104.39 98.86 858.32 127.41 98.65
3 3580.37 1242.23 97.62 3437.55 1300.1 96.82
4 3344.41 163 99.05 3181.6 246.46 98.83
5 1637.53 82.27 98.77 1566.48 142.8 98.82
6 2258.44 869.57 97.33 2193.74 1123.25 82.12
7 1896.20 898.28 97.86 1881.40 943.13 97.58
8 2443.10 210.66 99.09 2262.16 278.49 98.79
9 2435.14 460.57 97.63 2417.06 559.23 97.37
10 1522.83 535.35 95.63 1410.74 610.25 92.21
11 1025.56 303.35 98.75 1023.25 308.44 98.81
EEBH, end expiration breath hold; PG, phased gating; GTV, gross tumor volume; PTV, planned target volume.

Table 2. Proportions of healthy liver receiving > 15 Gy for EEBH and PG

Patient EEBH EEBH Proportion PG Liver- PG Liver- Proportion
Number Liver-GTV Liver-GTV of liver- GTV GTV of liver-
Volume Volume > GTV Volume Volume > GTV
(cm3) 15 Gy getting > (cm3) 15Gy (cm3) getting >
(cm3) 15 Gy for 15 Gy for
EEBH PG
1 1658.44 180.36 0.1087 1590.10 382.60 0.2406
2 949.46 104.39 0.1099 858.32 127.41 0.1484
3 3580.37 1242.23 0.3469 3437.55 1300.1 0.3782
4 3344.41 163 0.0487 3181.6 246.46 0.0774
5 1637.53 82.27 0.0502 1566.48 142.8 0.0911
6 2258.44 869.57 0.3850 2193.74 1123.25 0.5120
7 1896.20 898.28 0.4737 1881.40 943.13 0.5012
8 2443.10 210.66 0.0862 2262.16 278.49 0.1231
9 2435.14 460.57 0.1891 2417.06 559.23 0.2313
10 1522.83 535.35 0.3515 1410.74 610.25 0.4325
11 1025.56 303.35 0.2957 1023.25 308.44 0.3014
EEBH, end expiration breath hold; PG, phased gating; GTV, gross tumor volume; PTV, planned target volume.