1

A comparison of single-phase and phase-gated average verification planning for proton

radiotherapy
Katelyn Knoepke, BS, R.T.(R)(T), Jennifer DeWeese, BS, R.T.(R)(T), Joseph Spencer, BS, R.T.
(R)(T)(CT), Nishele Lenards, PhD, CMD, R.T.(R)(T), FAAMD, Ashley Hunzeker, MS, CMD,
Jedediah E. Johnson, PhD
Medical Dosimetry Program at the University of Wisconsin-LaCrosse, WI
ABSTRACT
To address challenges and enhance the efficiency of online adaptive radiation therapy,
advancements in automation are pivotal. The problem is that the verification process for phase-
gated treatments requires the creation of a new phase-gated average scan which is time-
consuming and incompatible with current workflows utilizing automated software. Therefore,
the purpose of this study was to compare the target coverage (specified as V95%) on a single, full
exhale phase verification plan will be within 5% of the target coverage (V95%) on a phase-gated
average verification plan to determine whether a single-phase verification is an acceptable
surrogate. Quantitative analysis supported the hypothesis, showing target coverage differences
within 5% for lung, liver, and esophagus patients, with small specific differences highlighting
clinical viability, and qualitative analysis indicated consistent clinical decisions, despite minor
discrepancies, especially in lung and liver cases. The study suggests that single-phase verification
plans can be acceptable surrogates for phase-gated plans, improving efficiency in proton therapy
practice, with considerations based on clinical scenarios and motion characteristics.
Keywords: Proton therapy; 4DCT; verifications; interplay; adaptive radiation therapy; phase-
gated
Introduction
The advantages of proton pencil beam radiotherapy over conventional x-ray radiotherapy
have led to a growing interest in its application. Proton treatments generally deliver less integral
dose to surrounding healthy organs, resulting in better treatment outcomes.1,2 However, the
primary challenge of proton pencil beam treatments lies in the sensitivity of the planned dose
distribution to changes in proton range, making these plans vulnerable to degradation due to
changes in patient anatomy.3,4,5 Daily variations in patient setup and anatomical changes can alter
the dose distribution, affecting both target coverage and organs at risk (OAR) sparing.1,3 To
manage these uncertainties and ensure the ongoing safety and effectiveness of the proton therapy
 2

treatments, acquiring routine CT verification scans is essential.1 The CT verification is performed

under the same scanning parameters as the CT simulation. The treatment plan is recalculated on
the CT verification image set, allowing for a quantitative assessment of the dose on current
patient anatomy. These regular scans help assess any deviations in the current dose distribution
from the initial treatment plan, enabling clinical interventions such as the creation of a modified
treatment plan.2,6,7 This replanning may be necessary through the course of treatment, especially
beyond 4 weeks, emphasizing the importance of an efficient verification and replanning process
to maintain plan quality.1,4,6,8
Another significant challenge of proton pencil beam therapy is the impact of respiratory
motion, which can introduce interplay effects that produce suboptimal dose distributions. 2,3,5,9
The interplay effect occurs because of the relative motion between a dynamic treatment delivery
and a moving target.5 Some spots are placed closer together than intended, while others are
pulled further apart, increasing dose heterogeneity.2 Furthermore, respiratory motion can also
lead to tissue changes upstream of the intended target, causing corresponding changes in the
proton range and affecting the resulting delivered dose to the target.2,10
Utilization of four-dimensional computed tomography (4DCT) imaging is a standard
technique for motion evaluation and treatment planning for mobile targets using pencil beam
proton therapy.2,8,10 Four-dimensional image sets are created by tracking the position of a
surrogate marker and correlating this signal with an oversampled CT image set that captures the
full respiratory cycle at each anatomical location. This 4D reconstruction results in 10 separate
three-dimensional computed tomography (3DCT) data sets, each representing a portion of the
breathing cycle and allowing for characterization of target motion.2,8 If this motion amplitude
results in a treatment plan with an unacceptably large volume of healthy tissue irradiation and/or
interplay effect, a respiratory-gated technique can be used. In a phase-gated approach, only a
subset of the breathing phases surrounding full exhale are averaged together and used for
treatment planning.2,8,9 The corresponding treatment is only delivered during these breathing
phases by actively gating the beam using the breathing surrogate signal.2,8
In modern radiation therapy, the demand for streamlined and efficient workflows is
paramount, particularly when dealing with phase-gated patients and the ever-advancing online
adaptive radiation therapy (ART). When a verification scan is performed on a phase-gated
patient, a new phase-gated data set must be generated. The manual process of creating a new
 3

phase-gated image set involves a full 4D reconstruction and customized averaging of the
individual breathing phases. With clinical efficiency in proton clinics at a premium, this presents
an opportunity for further process optimization. This is especially important in the motivation
toward automation in online ART, which involves real-time dose assessment and subsequent
modification of the treatment plan to maximize target dose and minimize normal tissue
dosage.1,4,7,11 Adaptive radiation therapy is especially beneficial during hypofractionated
treatments because of the increased relative importance of each fraction. Online ART is
performed in the treatment room immediately prior to treatment delivery and is particularly
suitable for treatment areas with anticipated adaption needs, such as intra-abdominal
sites.2,7 Efficient workflows are crucial for implementing online adaptive protocols in
radiotherapy practices, which involve complex and labor-intensive tasks such as imaging,
assessment, replanning, and quality assurance.7,11 Decreased efficiency can lead to targeting
inaccuracies due to changes between initial imaging and beam delivery.2
To address these challenges and enhance the efficiency of online adaptive radiation
therapy, advancements in automation are pivotal. The problem is that the verification process for
phase-gated treatments requires the creation of a new phase-gated average scan which is time-
consuming and incompatible with current workflows utilizing automated software. Therefore,
the purpose of this study was to compare the target coverage (specified as V95%) onbetween a
single, full exhale phase verification plan will be within 5% of the target coverage (V95%) onand a
phase-gated average verification plan to determine whether a single-phase verification is an
acceptable surrogate. Researchers hypothesized that the target coverage of the rigid, deformable,
and physician-modified CTVs will be within 5% of the target coverage V95% for the studied lung
(H1A), liver (H2A) and esophageal (H3A) patients. Additionally, researchers hypothesized that the
single-phase verification and phase-gated average verification comparison of CTV target
coverage will differ by no more than 5% of original plans and adaptive replans (H4A). If a single-
phase scan is suitable, it will improve current online, pre-treatment dose verification efforts for
phase-gated proton treatments by providing a timely, automated result which can be evaluated
prior to treatment by care teams while the patient is still in treatment position. Researchers
hypothesized that the target coverage of the rigid, deformable, and physician-modified CTVs
will be within 5% of the target coverage V95% for the studied lung (H1A), liver (H2A) and
esophageal (H3A) patients.
 4

Methods and Materials

Patient Selection
This study included datasets of patients that had received phase-gated intensity-
modulated proton therapy (IMPT) treatment and completed at least one 4D verification scan
throughout the treatment course. In each case, initial tumor motion was assessed during a 4D
simulation process and was found to be greater than 10.0 mm, which is an indication for phase-
gated treatment in our clinic. A member of the physics team reviewed the scans and determined
the phase range across which to create the phase-gated average scan that was used during
treatment and planning. Anatomic treatment sites included in this study were lung, liver, and
esophagus. Excluded from this study were datasets that were not within the included treatment
sites as well as those not utilizing phase-gated treatment delivery. The selection of verification
scans for our research was carried out through a random sampling method, with the aim of
capturing instances of scans that were either replanned due to inadequate target coverage or
retained without any alterations due to sufficient target coverage. The final study population
included 18 patients with a site breakdown of 7 esophagus, 6 lung, and 5 liver patients.
Verification Process
For each patient selected, the verification process was completed to create both a phase-
gated average verification along with a single-phase verification. Each of the patients in this
study received a weekly 4DCT verification scan, with one of these weekly scans designated for
this analysis. The 4D image set was sub-divided into 10 respiratory phases. For the phase-gated
verification, a phase-gated average scan was created utilizing the same phase selection from
initial treatment planning. For this study, the single-phase verification data set included only the
50-phase from the 4D data set.
Each of these data sets was individually sent to MIM Maestro (MIM) for processing. A
MIM workflow, which included a manual registration process and the creation of rigid and
deformable contours, was performed on each data set. A rigid and deformable CTV contour
was created for each high and low dose CTV. Registration was based on daily image guided
radiation therapy (IGRT) matching instructions which were patient dependent and instructed the
radiation therapists how to match the patient on a daily basis. For this reason, the verification
scan had to mimic how the patient was matched on the treatment machine. The original contours
were both rigidly and deformably transferred from the original simulation scan to the verification
 5

scan. The verification scan and contours were transferred with from MIM and imported into
treatment planning software Eclipse 15.6 (Varian Medical Systems, Inc.). A verification plan
was completed by calculating the original treatment plan on the new verification data set. Each
plan was then checked verified by a physicist for accuracy and then reviewed by the physician.
Physician Review
A new CTV contour was created by the physician to accurately delineate the target on
both the original phase-gated average data set as well as the 50-phase. This resulted in a new
target contour on both data sets that was more accurate than the rigid and deformable CTV
obtained through the verification process. The CTV contour from the phase-gated average data
set was also copied to the 50-phase image for target coverage comparison. This process was
completed for lung and esophagus patients. Liver patients did not have a new CTV contour
created due to the lack of magnetic resonance imaging (MRI) necessary to delineate target
volumes.
Following CTV modifications, Tthe physician performed a side-by-side evaluation of the
phase-gated and 50-phase verification for each patient. Any significant differences between the
two 2 verification plans were noted. The physician determined if the clinical decision regarding
the plan acceptability and the need for replanning would vary between the two verifications.
Data Collection and Statistical Analysis
To assess target coverage between the phase-gated and single-phase scans, the V95% was
evaluatedData collection involved obtaining the V95% for the rigidly, transferred contours, the
deformably, transferred contours, and the physician-modified physician contours for both the
high and low dose CTV on both the single-phase and phase-gated verification plan for each
patient. To compare the target coverage between the single-phase and phase-gated verification, a
dependent t-test was performed. The mean difference in target coverage between the single-
phase and phase-gated average verification was assessed along with the pP-value and 95%
confidence interval. Data was examined within various cohorts including a comprehensive
cohort as well as groupings by disease site and replan requirement.
Results
Comprehensive Cohort Comparison
When analyzing the comprehensive cohort of treatment sites, the mean difference in
target coverage (V95%) between the phase-gated average verification and single-phase verification
 6

was assessed for the rigid, deformable, new phase-gated, and new single-phase CTV structures
(Table 1). The mean difference in target coverage for the rigid CTV contour between the phase-
gated average verification and the single-phase verification (n=30) was - 0.46% ± 1.1%
(P=0.030) with a 95% CI [- 0.87, - 0.05]. The mean difference in target coverage for the
deformable CTV contour between the phase-gated average verification and the single-phase
verification (n=30) was - 0.13% ± 1.7% (P=0.683) with a 95% CI [- 0.77,0.51]. The mean
difference in target coverage for the new phase-gated CTV contour between the phase-gated
average verification and the single-phase verification (n=20) was - 0.63% ± 1.3% (P=0.471) with
a 95% CI [- 1.26, - 0.01]. The mean difference in target coverage between the new phase-gated
CTV contour on the phase-gated verification and the new single-phase CTV contour on the
single-phase verification (n=20) was - 0.45% ± 1.3% (P=0.139) with a 95% CI [- 1.07,0.16]. The
mean difference in target coverage between the phase-gated average verification and the single-
phase verification was within 5% for each contour evaluated when considering the
comprehensive cohort of treatment sites. (Figure 1)
Lung Patient Comparison
The mean difference in target coverage (V95%) between the phase-gated average
verification and single-phase verification was assessed for the rigid, deformable, new phase-
gated, and new single-phase CTV structures was also assessed for each treatment site
individually. The lung patient population had a mean difference in target coverage for the rigid
CTV contour between the phase-gated average verification and the single-phase verification
(n=7) of - 1.72% ± 1.8% (P=0.043) with a 95% CI [- 3.36, - 0.07]. The mean difference in target
coverage for the deformable CTV contour between the phase-gated average verification and the
single-phase verification (n=7) was - 1.13% ± 2.2% (P=0.220) with a 95% CI [- 3.15, 0.89]. The
mean difference in target coverage for the new phase-gated CTV contour between the phase-
gated average verification and the single-phase verification (n=7) was - 1.67% ± 1.9% (P=0.057)
with a 95% CI [- 3.41, 0.07]. The mean difference in target coverage between the new phase-
gated CTV contour on the phase-gated verification and the new single-phase CTV contour on the
single-phase verification (n=7) was - 1.08% ± 2.2%. (P=0.234) with a 95% CI [- 3.08, 0.92]. The
mean difference in target coverage between the phase-gated average verification and the single-
phase verification was within 5% for each contour evaluated for the lung patient cohort. (Figure
2)
 7

Liver Patient Comparison

The liver patient population had a mean difference in target coverage (V95%) for the rigid
CTV contour between the phase-gated average verification and the single-phase verification
(n=10) of 0.03% ± 0.2% (P =0.593) with a 95% CI [- 0.11, 0.17]. The mean difference in target
coverage for the deformable CTV contour between the phase-gated average verification and the
single-phase verification (n=10) was 0.94% ± 1.3% (P=0.052) with a 95% CI [- 0.01, 1.88]. This
patient population did not have the CTV recontoured on the verification data sets due to inability
to delineate target volumes in absence of more advanced imaging. The mean difference in target
coverage between the phase-gated average verification and the single-phase verification was
within 5% for each contour evaluated for the liver patient cohort (Figure 3).
Esophagus Patient Comparison
The esophagus patient population had a mean difference in target coverage (V95%) for the
rigid CTV contour between the phase-gated average verification and the single-phase
verification (n=13) of - 0.16% ± 0.3% (P=0.053) with a 95% CI [- 0.32, 0]. The mean difference
in target coverage for the deformable CTV contour between the phase-gated average verification
and the single-phase verification (n=13) was - 0.41% ± 1.3% (P=0.288) with a 95% CI [- 1.21,
0.39]. The mean difference in target coverage for the new phase-gated CTV contour between the
phase-gated average verification and the single-phase verification (n=13) was - 0.07% ± 0.3%
(P=0.328) with a 95% CI [- 0.22, 0.08]. The mean difference in target coverage between the new
phase-gated CTV contour on the phase-gated verification and the new single-phase CTV contour
on the single-phase verification (n=13) was - 0.12% ± 0.3 (P=0.124) with a 95% CI [- 0.27,
0.04]. The mean difference in target coverage between the phase-gated average verification and
the single-phase verification was within 5% for each contour evaluated for the esophagus patient
cohort (Figure 4).
Replan Status Comparison
Verification plans were divided into 2 separate cohorts depending on whether the initial
phase-gated verification did or did not indicate the need for a replan. The mean difference in
target coverage (V95%) was assessed within these cohorts to determine if this distinction made a
difference in target coverage between the phase-gated verification and single-phase verification.
The verification plans that did required a replan had a mean difference in target coverage for the
rigid CTV contour between the phase-gated average verification and the single-phase
 8

verification (n=10) of - 1.07% ± 1.72% (P=0.080) with a 95% CI [- 2.3, 0.16]. The mean
difference in target coverage for the deformable CTV contour between the phase-gated average
verification and the single-phase verification (n=10) was - 1.15%± 2.25% (P=0.140) with a 95%
CI [- 2.77,0.46]. The mean difference in target coverage for the new phase-gated CTV contour
between the phase-gated average verification and the single-phase verification (n=8) was -
1.34% ± 1.9% (P=0.079) with a 95% CI [- 2.89, 0.21]. The mean difference in target coverage
between the new phase-gated CTV contour on the phase-gated verification and the new single-
phase CTV contour on the single-phase verification (n=8) was - 0.65% ± 2.0%. (P=0.379) with a
95% CI [- 2.3, 0.99]. The mean difference in target coverage between the phase-gated average
verification and the single-phase verification was within 5% for each contour evaluated for the
verifications requiring a replan cohort (Figure 5).
The verification plans that did not require a replan had a mean difference in target
coverage (V95%) for the rigid CTV contour between the phase-gated average verification and the
single-phase verification (n=20) of - 0.15% ± 0.4% (P=0.088) with a 95% CI [- 0.33, 0.03]. The
mean difference in target coverage for the deformable CTV contour between the phase-gated
average verification and the single-phase verification (n=20) was 0.38% ± 1.1% (P=0.138) with
a 95% CI [- 0.13, 0.9]. The mean difference in target coverage for the new phase-gated CTV
contour between the phase-gated average verification and the single-phase verification (n=12)
was - 0.16% ± 0.5% (P=0.313) with a 95% CI [- 0.49, 0.17]. The mean difference in target
coverage between the new phase-gated CTV contour on the phase-gated verification and the new
single-phase CTV contour on the single-phase verification (n=12) was - 0.32% ± 0.7%.
(P=0.137) with a 95% CI [- 0.76, 0.12]. The mean difference in target coverage was within 5%
for each contour evaluated for the sample of verifications not resulting in re-planning (Figure 6).
The hypothesis was that the target coverage of the rigid, deformable, and physician-
modified CTVs would be within 5% of the target coverage V95% for the studied lung (H1A), liver
(H2A) and esophageal (H3A) patients. Mean difference in target coverage was within 5% for all
contours evaluated within each cohort with the 95% CI falling within 5%: therefore, the null
hypothesis (H10) was rejected.
Discussion
The results of the quantitative analysis demonstrated that the mean difference in target
coverage (V95%) between the phase-gated average verification plans and single-phase verification
 9

plans was within 5% for all contours evaluated, irrespective of treatment site or replanning
status. The statistical significance indicated by the pP-value varied amongst cohorts and the
contour used for evaluation. Small differences between the two 2 groups along with a limited
sample size resulted in non-significance. However, the 95% confidence interval validated that the
difference in target coverage between a phase-gated average verification and a single-phase
verification should be within 5%. This finding is crucial as it supports the hypothesis that single-
phase verification plans are acceptable surrogates for phase-gated plans. This result has
significant clinical implications for proton therapy practice. By using single-phase verification,
proton therapy clinics can reduce the time and resource requirements associated with phase-gated
scans and streamline their treatment process. This is particularly pertinent in the context of online
adaptive radiation therapy, where real-time adjustments to treatment plans are essential.
The specific values of mean differences were also generally small, further underscoring
the clinical viability of single-phase verification plans. The data indicate that the difference in
target coverage is not clinically significant in an overall sense, and should not necessitate
different clinical decisions, such as replanning. This notwithstanding, there may be specific cases
in which the clinical goals require a tighter degree of correspondence, at the discretion of the
attending physician. These findings are particularly relevant for lung, liver, and esophagus
patients who often require phase-gated treatment due to respiratory motion. The results show that
single-phase verification plans generally provide clinically acceptable representations of the
target coverage in phase-gated plans for these patients, potentially streamlining the treatment
process and reducing the need for resource-intensive phase-gated scans.
A site group physician reviewed both the original phase-gated verification along with the
newly generated single-phase verification. They elaborated on whether encountering either
version would lead to a different clinical decision. For instance, reconsidering the need for a
replan, introducing an extra verification, or conveying specific instructions to therapists
regarding the setup process. Any significant differences between the verifications were noted.
The lung patient population consisted of 6 patients, of which 4 were replanned. For 2 of
these patients, the physician noted similar target coverage with an identical clinical decision
regarding replanning between the phase-gated average verification and the single-phase
verification. Three patients had a decrease in target coverage on the single-phase verification.
However, in two of these cases the clinical decision would not have been changed. One case
 10

would require a replan that was not indicated on the original verification. The final case the
physician felt unable to assess using the single-verification due to diaphragm motion
considerations. The liver patient population consisted of 5 patients, of these 1 was replanned. The
case requiring replanning showed similar insufficient coverage and hot spots on both verification
plans. An equivalent decision to replan would have resulted in either scenario. One case showed
a decrease in coverage near the dome of the liver that was not present on the original phase-gated
verification. This would have triggered an additional verification that was not originally
requested. For all other patients, the original phase-gated verification and new single-phase
verification were similar and showed that the plans held up. The esophagus patient population
consisted of 7 patients, of these 2 were replanned. All esophagus evaluations resulted in
equivalent clinical decisions from the physician.
The qualitative analysis revealed overall consistency in clinical decisions between the
single-phase and phase-gated verification plans, aligning with the assertion in the results section
that all averages were below the 5% threshold, indicating an acceptable surrogate. In many cases,
the single-phase verification plans supported the same clinical decisions as the phase-gated
plans, even in scenarios where there was a minor decrease in target coverage. There were a few
instances where the single-phase verification plans led to different clinical decisions. These
discrepancies were primarily observed in lung patients and, in 1 case, for a liver patient.
However, it becomes apparent that the few instances where clinical decisions differed, the
assertion that all averages were below 5% might oversimplify the clinical reality, as even minor
variations could potentially impact management decisions.
For the lung patients, in most instances, the differences in coverage were clinically
acceptable and would not necessitate a change in the treatment plan. However, the researchers
identified 1 case where the diaphragm motion influenced the assessment, suggesting that the
choice between single-phase and phase-gated verification might depend on the specific clinical
scenario and motion characteristics. The liver patient with a decrease in coverage in the dome of
the liver highlights a situation where the single-phase verification could have led to a different
clinical decision, such as an additional verification or replanning. While this was a single case, it
underscores the need for a case-by-case assessment to ensure the appropriateness of using single-
phase verification for liver patients. For esophagus patients, the clinical decisions remained
 11

consistent between single-phase and phase-gated verification plans, indicating that for certain
anatomical sites, single-phase verification may be a suitable option.
Conclusion
Proton pencil beam radiotherapy is gaining popularity due to its superior sparing of
healthy organs compared to conventional x-ray radiotherapy. However, it is vulnerable to
changes in patient anatomy and the impact of respiratory motion, necessitating routine CT
verification scans in phase-gated plans. The problem is that the verification process for phase-
gated treatments requires the creation of a new phase-gated average scan which is time-
consuming and incompatible with current workflows utilizing automated software The primary
objective of the study was to assess whether single-phase verification plans could effectively
substitute phase-gated plans by comparing target coverage. Both qualitative and quantitative
analyses were conducted to evaluate the suitability of single-phase verification plans. The results
suggest that single-phase verification plans offer a clinically viable and efficient alternative to
phase-gated plans in proton therapy.
The limitations of this study included a relatively small sample size and a focus on
specific treatment sites, potentially limiting the generalizability of the results. Future research
should expand the patient population to include a broader range of treatment sites, investigate the
impact of varying motion characteristics on verification plan suitability, and explore automated
processes for generating single-phase verification plans. These endeavors can further enhance the
efficiency and accessibility of proton therapy while addressing the identified limitations of this
study.
Acknowledgements
The authors would like to thank Douglas Baumann and the UW-La Crosse Statistical Consulting
Center for their guidance with data analysis and display of statistical results for the study. Any
errors in statistics or interpretation of data are the sole responsibility of the authors.
 12

References
1. Deiter N, Chu F, Lenards N, Hunzeker A, Lang K, & Mundy D. Evaluation of replanning
in intensity-modulated proton therapy for oropharyngeal cancer: Factors influencing plan
robustness. Med Dosim. 2020;45(4):384-392.
https://doi.org/10.1016/j.meddos.2020.06.002
2. Tryggestad EJ, Liu W, Pepin MD, Hallemeier CL, & Sio TT. Managing treatment-related
uncertainties in proton beam radiotherapy for gastrointestinal cancers. J of Gastrointest
Oncol. 2020;11(1):212-224. https://doi.org/10.21037/jgo.2019.11.07
3. Knäusl B, Lebbink F, Fossati P, Engwall E, Georg D, Stock M. Patient breathing motion
and delivery specifics influencing the robustness of a proton pancreas irradiation.
Cancers. 2023;15(9):2550. https://doi.org/10.3390/cancers15092550
4. Hu YH, Harper, RH, Deiter NC, et al. Analysis of the rate of re-planning in spot-scanning
proton therapy. Int J of Part Ther. 2022;9(2):49-58. https://doi.org/10.14338/IJPT-21-
00043.1
5. Smolders A, Hengeveld AC, Both S, et al. Inter- and intrafractional 4D dose
accumulation for evaluating ΔNTCP robustness in lung cancer. Radiother Oncol.
2023;182:109488. https://doi.org/10.1016/j.radonc.2023.109488
6. Evans JD, Harper RH, Petersen M, et al. The importance of verification CT-QA scans in
patients treated with IMPT for head and neck cancers. Int J of Part Ther. 2020;7(1):41-
53. https://doi.org/10.14338/IJPT-20-00006.1
7. Green OL, Henke LE, & Hugo GD. Practical clinical workflows for online and offline
adaptive radiation therapy. Semin in Radiat Oncol.
2019;29(3):219-227. https://doi.org/10.1016/j.semradonc.2019.02.004
8. Gelover E, Deisher AJ, Herman MG, Johnson J E, Kruse JJ, & Tryggestad EJ. Clinical
implementation of respiratory‐gated spot‐scanning proton therapy: an efficiency analysis
of active motion management. J of Appl Clin Med Phys.
2019;20(5):99-108. https://doi.org/10.1002/acm2.12584
9. Gut P, Krieger M, Lomax T, Weber DC, & Hrbacek J. Combining rescanning and gating
for a time-efficient treatment of mobile tumors using pencil beam scanning proton
therapy. Radiother Oncol. 2021;160: 82-89.
https://doi.org/10.1016/j.radonc.2021.03.041
 13

10. Taasti VT, Hattu D, Vaassen F, et al. Treatment planning and 4D robust evaluation
strategy for proton therapy of lung tumors with large motion amplitude. Med Phys.
2021;48(8):4425-4437. https://doi.org/10.1002/mp.15067

11. Paganetti H, Botas P, Sharp GC, Winey B. Adaptive proton therapy. Phys in Med & Biol.
2021;66(22). https://doi.org/10.1088/1361-6560/ac344f
 14

Figures

Figure 1. Difference in target coverage (V95%) for comprehensive treatment site cohort.

Figure 2. Difference in target coverage (V95%) for lung cohort.

 15

Figure 3. Difference in target coverage (V95%) for liver cohort.

Figure 4. Difference in target coverage (V95%) for esophagus cohort.

 16

Figure 5. Difference in target coverage (V95%) for cohort initially requiring a replan.

Figure 6. Difference in target coverage (V95%) for cohort not initially requiring a replan.
 17

Tables
Table 1. Mean Difference in Target Coverage (V95%).
Mean Standard 95% p-value
Difference (%) Deviation Confidence
Interval
All Sites
Rigid Contour -0.46 1.1 [-0.87, -0.05] 0.030
Deformable Contour 0.13 1.7 [-0.77, 0.51] 0.683
New Phase-gated contour -0.63 1.3 [-1.26, -0.01] 0.471
New Phase-gated vs. New Single- -0.45 1.3 [1.07, 0.16] 0.139
phase contour

Lung
Rigid Contour -1.72 1.8 [-3.36, -0.07] 0.043
Deformable Contour -1.13 2.2 [-3.15, 0.89] 0.220
New Phase-gated contour -1.67 1.9 [-3.41, 0.07] 0.057
New Phase-gated vs. New Single- -1.08 2.2 [-3.08, 0.92] 0.234
phase Contour

Liver
Rigid Contour 0.03 0.2 [-0.11, 0.17] 0.593
Deformable Contour 0.94 1.3 [-0.01, 1.88] 0.052

Esophagus
Rigid Contour -0.16 0.3 [-0.32, 0] 0.053
Deformable Contour -0.41 1.3 [-1.21, 0.39] 0.288
New Phase-gated contour -0.07 0.3 [-0.22, 0.08] 0.328
New Phase-gated vs. New Single- -0.12 0.3 [-0.27, 0.04] 0.124
phase Contour

Re-Plan
Rigid Contour -1.07 1.7 [-2.3, -0.16] 0.080
Deformable Contour -1.15 2.3 [-2.77, 0.46] 0.140
New Phase-gated contour -1.34 1.9 [-2.89, 0.21] 0.079
New Phase-gated vs. New Single- -0.65 2.0 [-2.3, 0.99] 0.379
phase Contour

No Re-Plan
Rigid Contour -0.15 0.4 [-0.33, 0.03] 0.088
Deformable Contour 0.38 1.1 [-0.13, 0.9] 0.138
New Phase-gated contour -0.16 0.5 [-0.49, 0.17] 0.313
New Phase-gated vs. New Single- -0.32 0.7 [-0.76, 0.12] 0.137
phase Contour
18