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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
I. Abstract
II. Introduction
A. PI: Proton beam advantages, sensitivity to patient changes, CT verification for
treatment accuracy and adjustments. (Reference: Deiter et al,1 Tryggestad et al,2
Knäusl et al,3 Hu et al,4 Smolders et al,5 Evans et al,6 Green et al,7 Gelover et al8)
B. PII: Challenges due to respiratory motion, interplay effects and dose distribution
issues. (Reference: Tryggestad et al,2 Knäusl et al,3 Smolders et al,5 Gut et al,9 Tassti el
al10)
C. PIII: 4DCT imaging for target motion, respiratory gating for interplay effects.
(Reference: Tryggestad et al,2 Gelover et al,8 Gut et al,9 Tassti el al10)
D. PIV: The need for efficiency and optimization, adaptive radiation therapy, and
treatment accuracy while minimizing normal tissue exposure during hypofractionated
treatments. (Reference: Deiter et al,1 Tryggestad et al,2 Hu et al,4 Green et al,7
Paganetti et al11)
E. PV: Summarize introduction points.
1. Problem: 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.
2. Purpose: The purpose of this study was to compare target coverage reported on
phase-gated average verification plans to target coverage on single-phase
verification plans using the same plan to determine whether a single-phase
verification is an acceptable surrogate.
3. Hypothesis: The first research hypothesis (H1) is that 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 for all
sites based on evaluation of rigid, deformable, and newly created target contours.
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Also, this will be true within each treatment site individually, as well as within
groups based on replan requirement.
III. Materials and Methods
A. PI: Patient selection
1. Patient selection criteria
a. Inclusion criteria (phase-gated treatment, at least one verification, included
sites)
b. Exclusion criteria (non phase-gated treatment, not included treatment sites)
2. Study Population
a. Number of patients (18)
b. Lung patients (6)
c. Liver patients (5)
d. Esophagus patients (7)
B. PII-III: Verification Process
1. Data-set creation
a. Phase-gated average
b. Single-phase
2. Verification plan creation
a. MIM workflow
b. Eclipse import and verification plan process
c. Physics and physician review
C. PIV-V: Physician Review
1. Contour creation
2. Evaluation
D. PVI: Data Collection and Statistical Analysis
1. Dose statistics
2. T-test for dependent means
3. Evaluation cohorts
IV. Results
A. PI: Comprehensive Cohort Comparison (Quantitative Analysis)
1. All treatment sites (Table 1, Figure 1)
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a. Rigid CTV contour (n=30): mean difference is -0.46% ± 1.1% (p=0.030)

b. Deformable CTV contour (n=30): mean difference is –0.13% ± 1.7%
(p=0.683)
c. New phase-gated CTV contour (n=20): mean difference is –0.63% ± 1.3%
(p=0.471)
d. New phase-gated vs. New 50-phase contour (n=20): mean difference is 0.45%
± 1.3% (p=0.139)
e. Target coverage (V95%) is within ± 5% for all contours
2. PII: Lung Patient Comparison (Figure 2)
a. Rigid CTV contour (n=7): mean difference is –1.72% ± 1.8% (p= 0.043)
b. Deformable CTV contour (n=7): mean difference is -1.13%± 2.2% (p=0.220)
c. New phase-gated CTV contour (n=7): mean difference is –1.67% ± 1.9%
(p=0.057)
d. New phase-gated vs. New 50-phase contour (n=7): mean difference is –1.08%
± 2.2%. (p=0.234)
e. Target coverage (V95%) is within ± 5% for all contours
3. PIII: Liver Patient Comparison (Figure 3)
a. Rigid CTV contour (n=10): mean difference is 0.03% ± 0.2% (p= 0.593)
b. Deformable CTV contour (n=10): mean difference is 0.94% ± 1.3% (p=
0.052)
c. Target coverage (V95%) is within ± 5% for all contours
4. PIV: Esophagus Patient Comparison (Figure 4)
a. Rigid CTV contour (n=13): mean difference is –0.16% ± 0.3% (p=0.053)
b. Deformable CTV contour (n=13): mean difference is –0.41% ± 1.3%
(p=0.288)
c. New phase-gated CTV contour (n=13): mean difference is –0.07% ± 0.3%
(p=0.328)
d. New phase-gated vs. New 50-phase contour (n=13): mean difference is –
0.12% ± 0.3%. (p=0.124)
e. Target coverage (V95%) is within ± 5% for all contours
5. PV: Replan Status Comparison (Figure 5)
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a. Rigid CTV contour (n=7): mean difference is –0.75% ± 1.1% (p= 0.120)
b. Deformable CTV contour (n=7): mean difference is -1.02%± 2.4% (p=0.313)
c. New phase-gated CTV contour (n=8): mean difference is –1.34% ± 1.9%
(p=0.079)
d. New phase-gated vs. New 50-phase contour (n=8): mean difference is –0.65%
± 2.0%. (p=0.379)
e. Target coverage (V95%) is within ± 5% for all contours
6. PVI: No Replan (Figure 6)
a. Rigid CTV contour (n=20): mean difference is –0.15% ± 0.4% (p= 0.088)
b. Deformable CTV contour (n=20): mean difference is 0.38% ± 1.1% (p=0.138)
c. New phase-gated CTV contour (n=12): mean difference is –0.16% ± 0.5%
(p=0.313)
d. New phase-gated vs. New 50-phase contour (n=12): mean difference is –
0.32% ± 0.7%. (p=0.137)
e. Target coverage (V95%) is within ± 5% for all contours
7. PVII: Hypothesis evaluation
B. PVIII-IX: Qualitative Analysis
1. Physician review process
2. Results within each site group
a. Lung
b. Liver
c. Esophagus
V. Discussion
A. PI: Summarize purpose and findings
B. PII: Small mean differences support single-phase verification as viable for lung, liver,
and esophagus patients, streamlining proton therapy.
C. PIII: Single-phase verification plans align with clinical decisions but may vary
slightly, primarily for lung and liver patients.
D. PIV: Lung, liver, and esophagus findings
[E.] PV: Limitations of the study
[F.] PVI: Future research
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[VI.] Conclusion
E.[A.] PI: Summarize the study
1. Problem: 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.
2. Purpose: The purpose of this study was to compare target coverage reported on
phase-gated average verification plans to target coverage on single-phase
verification plans using the same scan to determine whether a single-phase
verification is an acceptable surrogate.
F.[B.] PII: Quantitative/Qualitative Analysis
G.[C.] PIII: Limitations/future research
1. Limitations: small sample size, specific treatment sites
2. Future research: expand patient populations, broader range of treatment sites,
explore automated processes.
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References
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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.
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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
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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
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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.
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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
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Figures

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

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

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

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

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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.
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Tables

Table 1. Mean Difference in Target Coverage (V95%).

Mean Standard p-value
Difference Deviatio
(%) n
All Sites
Rigid Contour -0.46 1.1 0.030
Deformable Contour –0.13 1.7 0.683
New Phase-gated contour -0.63 1.3 0.471
New Phase-gated vs. New Single-phase contour -0.45 1.3 0.139

Lung
Rigid Contour -1.72 1.8 0.043
Deformable Contour -1.13 2.2 0.220
New Phase-gated contour -1.67 1.9 0.057
New Phase-gated vs. New Single-phase Contour -1.08 2.2 0.234

Liver
Rigid Contour 0.03 0.2 0.593
Deformable Contour 0.94 1.3 0.052

Esophagus
Rigid Contour -0.16 0.3 0.053
Deformable Contour -0.41 1.3 0.288
New Phase-gated contour -0.07 0.3 0.328
New Phase-gated vs. New Single-phase Contour -0.12 0.3 0.124

Re-Plan
Rigid Contour -0.75 1.1 0.120
Deformable Contour -1.02 2.4 0.313
New Phase-gated contour -1.34 1.9 0.079
New Phase-gated vs. New Single-phase Contour -0.65 2.0 0.379

No Re-Plan
Rigid Contour -0.15 0.4 0.088
Deformable Contour 0.38 1.1 0.138
New Phase-gated contour -0.16 0.5 0.313
New Phase-gated vs. New Single-phase Contour -0.32 0.7 0.137