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Increasing inter-fraction target robustness in intensity-modulated proton radiotherapy for

lung cancer using a planning HU optimization structure
Carissa Rivinius BS, RT(R)(T); Kristen Dezell BS, RT(R)(T); Brittni McKane BS, RT(R)(T);
Nishele Lenards, PhD, CMD, RT(R)(T), FAAMD; Ashley Hunzeker, MS, CMD; Alan Kraling,
CMD, RT(T)

I. Abstract
II. Introduction
A. PI: Background of lung planning; introduction to IMPT and contributing factors
that play a role in target robustness for proton therapy (Reference: Grant et al,1
Zhang et al,2 Han,3)
B. PII: Inherent issues with thoracic dosimetry regarding tissue heterogeneities,
breathing motion, tumor growth or shrinkage that play a role in lung planning
(Reference: Grant et al,1 Han,3 Hranek et al,4)
C. PIII: Enhanced imaging technology such as 4DCT further improves dose accuracy
with setup errors along with geometric uncertainties related to motion (Reference:
Botas et al,5 Unkelbach et al,6)
D. PIV: 4DCT allows optimal target contouring and sparing of OAR, but inter-gate
motion requires layer-based repainting combined with 4D motion analyses to
further improve robustness (Reference: Botas et al,5 Johnson et al,7 Righetto et
al,8)
E. PV: Repainting, 4DCT, and improved algorithms increase robustness in IMPT
lung planning, but maintaining inter-fraction robustness remains a challenge;
research indicates benefits of an HU optimization structure covering the target
volume and lung overlap region (Reference: Botas et al,5 Tryggestad et al,9 Kang
et al,10 Liu et al,11)
F. PVI: Summarize introduction points and potential of an HU override to increase
IMPT inter-fraction robustness in lung planning
i. Problem: The problem is maintaining robust target coverage between the
target volume and lung overlap region due to inter-fraction tumor and
anatomy changes.
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ii. Purpose: The purpose of this study was to determine the value of an HU
optimization structure covering the target volume and lung overlap region
that will increase proton plan robustness and maintain the inter-fraction
target coverage.
iii. Hypotheses: The researchers tested that an HU optimization structure
using -400, -200, and 0 would increase original plan robustness of the
clinical target volume (CTV) such that 95% of the volume received at
least 100% or more of the prescribed dose (D95% ≥ 100%) for all
robustness curves (H1A, H2A, and H3A respectively) and maintain inter-
fraction CTV coverage D95% ≥ 95% (H4A, H5A, and H6A respectively).
III. Materials and Methods
A. Patient selection and Setup
i. PI: Inclusion and exclusion criteria
1. 15 retrospective cases from a single institution
2. Inclusion criteria: IMPT left lung targets with air in CTV overlap ≥
50 cm3, 5 verification scans throughout treatment, prescribed dose
of 60 Gy in 30 fractions to primary target
3. Exclusion criteria: Right lung targets, retreatments
ii. PII: Simulation procedures
1. 4DCT
B. Contouring
i. PI: Plan Details
1. Contour for CTV6000
2. Contours for OAR delineation (heart, lung, & esophagus)
3. Contour for HU optimization structure (Figure 1)
C. Treatment Planning
i. PI: Plan Setup
1. Eclipse TPS with NUPO algorithm
2. Single field optimization using re-paint vac machine
3. Field selection and number of beams
ii. PII: Plan Optimization
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1. Plans without and plans with HU optimization structure assigned

values of -400, -200, 0
2. Creation of DVH robustness curves for isocenter shifts and range
uncertainty
3. Original plans normalized to ensure least desirable robustness
curve maintained D95% ≥ 100%
D. Plan Evaluation
i. PI: Target evaluation
1. Original plan robustness reviewed
a. Extreme inspiration and expiration phases of 4DCT
reviewed
b. Evaluation of robustness curves for original plans verified
with weekly verification scans
c. CTV D95% ≥ 100%
2. Verification evaluation
a. CTV robustness within D95% ≥ 95%
E. Statistical Analysis
i. PI: Statistical analysis based on UW-LAX stats lab
1. Original plan robustness analysis using paired T-test
2. Inter-fraction plan robustness analysis using Wilcoxon Signed
Rank Test using the average of the 5 verification scans per patient
IV. Results
A. PI: Comparison of original plans with and without an HU optimization structure
to assess initial plan robustness of percentage of CTV6000 receiving 60 Gy
i. Original plan CTV metric without HU override for comparison to original
plan average using HU override per the paired T-test
ii. Verification CTV metric without HU override for comparison to
verification plan average using HU override per the WSR test
B. PII: -400 HU Results
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i. Original plan with an HU override value of -400 evaluating CTV6000

receiving 60 Gy metric (Figure 2), which suggested the existing null
hypothesis (H10) failed to be rejected.
ii. Verification scans with an HU override value of -400 evaluating CTV6000
receiving 60 Gy metric (Figure 3), which suggested the existing null
hypothesis (H40) was rejected.
C. PIII: -200 HU Results
i. Original plan with an HU override value of -200 evaluating CTV6000
receiving 60 Gy metric (Figure 2), which suggested the existing null
hypothesis (H20) failed to be rejected.
ii. Verification scans with an HU override value of -200 evaluating CTV6000
receiving 60 Gy metric (Figure 3), which suggested the existing null
hypothesis (H50) was rejected.
D. PIV: 0 HU Results
i. Original plan with an HU override value of 0 evaluating CTV6000
receiving 60 Gy metric (Figure 2), which suggested the existing null
hypothesis (H30) failed to be rejected.
ii. Verification scans with an HU override value of 0 evaluating CTV6000
receiving 60 Gy metric (Figure 3), which suggested the existing null
hypothesis (H60) was rejected.
V. Discussion
A. Result analysis
i. PI: Summarize CTV coverage differences between original and HU -400,
-200, 0 plans
ii. PII: Previous research and current findings
1. Current findings support previous research by Tryggestad et al9
regarding utilization of an HU override.
2. Summarize CTV coverage and inter-fraction robustness changes
with and without an HU override when viewing results of a single
patient from the research population (Figure 4)
B. Implications for medical dosimetry field
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i. PI: Inter-fraction plan robustness improved using an HU optimization

structure with an HU override of -400, -200, or 0
1. No superior HU value determined
2. Negligible increase in dose to OAR with HU override, findings
agree with Botas et al5 and Liu et al11
VI. Conclusion
A. Overall summary of the study
i. PI: Study objectives
1. Problem: The problem is maintaining robust target coverage
between the target volume and lung overlap region due to inter-
fraction tumor and anatomy changes.
2. Purpose: The purpose of this study was to determine the value of
an HU optimization structure covering the target volume and lung
overlap region that will increase proton plan robustness and
maintain the inter-fraction target coverage.
3. Hypotheses: The researchers tested that an HU optimization
structure using -400, -200, and 0 would increase original plan
robustness of the clinical target volume (CTV) such that 95% of
the volume received at least 100% or more of the prescribed dose
(D95% ≥ 100%) for all robustness curves (H1A, H2A, and H3A
respectively) and maintain inter-fraction CTV coverage D95% ≥
95% (H4A, H5A, and H6A respectively).
ii. PII: Study limitations
1. Small sample size (n = 15)
2. All patients collected from single institution using the same
treatment planning system (TPS) and dose calculation algorithm
iii. PIII: Future research
1. Larger sample size, expand inclusion criteria
a. Sample with more mobile targets near the diaphragm
b. Re-treatments
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2. Review of dose to OAR and statistical significance of inter-

fraction impact
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References

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in the design of anthropomorphic phantoms for proton radiotherapy. J Appl Clin Med
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2. Zhang X, Li Y, Pan X, et al. Intensity-modulated proton therapy reduces the dose to
normal tissue compared with intensity-modulated radiation therapy or passive scattering
proton therapy and enables individualized radical radiotherapy for extensive stage IIIB
non-small-cell lung cancer: a virtual clinical study. Int J Rad Oncol Biol Phys.
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4. Hranek A, Resch A, Georg D, Knäusl B. Investigation of the Bragg peak degradation
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5. Botas P, Grassberger C, Sharp G, Paganetti H. Density overwrites of internal tumor
volumes in intensity modulated proton therapy plans for mobile lung tumors. Phys Med
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10. Kang Y, Zhang X, Chang J, et al. 4D Proton treatment planning strategy for mobile lung
tumors. Int J Radiot Oncol Phys. 2007;67(3):906-914.
http://doi.org/10.1016/j.ijrobp.2006.10.045
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versus 3D robust optimization in intensity modulated proton therapy for lung cancer. Int
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Figures

Figure 1. This image shows a sample visual representation of a CTV volume without (A) and
with (B) an HU optimization structure in the axial (top), coronal (middle), and sagittal views
(bottom). The cyan color indicated by a striped arrow represents a CTV volume delineated by the
physician (A). The magenta color indicated by a solid black arrow represents the HU
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optimization structure along the lung and tissue interface created for this study (B), given an HU
override value of either -400, -200, or 0.
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Figure 2. Target coverage of original plans without and with HU override values of -400, -200,
and 0. Original plans without an HU optimization structure are represented by white. Original
plans using an HU optimization structure with an override value of -400 are shown as vertical
stripes, -200 are shown as dots, and 0 are shown as horizontal stripes.
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Figure 3. Target coverage of verification plans to assess inter-fraction robustness without and
with HU override values of -400, -200, and 0. Verification plans without an HU optimization
structure are represented in white. Verification plans using an HU optimization structure with an
override value of -400 are shown as vertical stripes, -200 are shown as dots, and 0 are shown as
horizontal stripes.
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Figure 4. Values obtained for statistical analysis without and with an HU optimization structure
for target plan robustness evaluation are shown above for one patient within the research
population. Original plans are shown first with a thick black border (white representing no
override, vertical stripes representing an override using HU -400, dots representing an override
using HU -200, and horizontal stripes representing an override using HU 0). Five associated
verification plans follow their corresponding original plan. Solid black represents any
verification plan that fell below robustness evaluation criteria.