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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, and even planning algorithms that
play a role in lung planning (Reference: Grant et al,1 Han,3 Hranek et al,4)
C. PIII: History of PBS calculation algorithm and improved robustness in lung
planning in relation to large air gaps; still, motion remains a challenge in
predicting accurate dose distribution (Reference: Grant et al, 1 Han,3 Botas et al,5)
D. PIV: Latest calculation algorithm combined with 4DCT further improves dose
accuracy with setup errors along with geometric uncertainties related to motion
(Reference: Botas et al,5 Unkelbach et al,6)
E. PV: 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)
F. PVI: 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)
G. PVII: Summarize introduction points and potential of an HU override to increase
IMPT inter-fraction robustness in lung planning
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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.
ii. Purpose: The purpose of this study was to determine the value of this HU
optimization structure that would increase proton plan robustness and
maintain inter-fraction target coverage.
iii. Hypotheses: The researchers tested an HU optimization structure using -
400 (H1A), -200 (H2A), and 0 (H3A) respectively to maintain robust inter-
fraction CTV coverage of D95% ≥ 100%. The researchers also tested an
HU optimization structure using -400 (H10), -200 (H20), and 0 (H30)
respectively resulting in not maintaining robust inter-fraction CTV
coverage of D95% ≥ 100%.
III. Materials and Methods
A. Patient selection
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 to primary target
3. Exclusion criteria: Right lung targets, retreatments
ii. PII: Simulation procedures
1. 4DCT
B. Treatment Planning
i. PI: Plan Details
1. Contours for HU optimization structure (Figure 1)
2. Contours for OAR delineation (heart, lung, & esophagus)
3. Eclipse TPS with NUPO algorithm
4. Single field optimization using re-paint vac machine
ii. PII: Plan Optimization
1. Field selection and number of beams
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2. Plan without and plans with HU optimization structure assigned

values of -400, -200, 0
3. Plan normalization based on target coverage and OAR constraints
C. Planning Evaluation
i. PI: Target evaluation
1. CTV D95% ≥ 95%
2. Least desirable robustness curves
a. Extreme inspiration and expiration phases
ii. PII: Verification evaluation
1. CTV robustness within D95% ± 5%
D. 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: Original plan CTV metrics (Figure 2)
i. CTV D95% original plan compared with HU -400, -200, 0 plans (Figure 3)
B. PII: Verification plan CTV metrics to assess inter-fraction robustness (Figure 4)
i. Average CTV D95% original plan compared with HU -400, -200, 0 plans
V. Discussion
VI. Conclusion
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References

1. Grant RL, Summers PA, Neihart JL, et al. Relative stopping power measurements to aid
in the design of anthropomorphic phantoms for proton radiotherapy. J Appl Clin Med
Phys 2014;(15):121-126. http://doi.org/10.1120/jacmp.v15i2.4523
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.
2010;77(2):357-366. http://doi.org/10.1016/j.ijrobp.2009.04.028
3. Han Y. Current status of proton therapy techniques for lung cancer. Radiat Oncol J.
2019;37(4):232-248. http://doi.org/10.3857/roj.2019.00633
4. Hranek A, Resch A, Georg D, Knäusl B. Investigation of the Bragg peak degradation
caused by homogeneous and heterogeneous lung tissue substitutes: proton beam
experiments and comparison to current clinical dose calculation. Phys Med Biol.
2020;65(24):1-11. http://doi.org/10.1088/1361-6560/abc938
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
Biol. 2018;63(3):035023. http://doi.org/10.1088/1361-6560/aaa035
6. Unkelbach J, Paganetti H. Robust proton treatment planning: Physical and biological
optimization. Semin Radiat Oncol. 2018;28(2):88-96.
http://doi.org/10.1016/j.semradonc.2017.11.005
7. Johnson JE, Herman MG, Kruse JJ. Optimization of motion management parameters in a
synchrotron-based spot scanning system. J Appl Clin Med Phys. 2019;20(9):69-77.
http://doi.org/10.1002/acm2.12702
8. Righetto R, Fracchiolla F, Widesott L, et al. Technical challenges in the treatment of
mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-
hold. Radiother Oncol. 2022;169:43-50. http://doi.org/10.1016/j.radonc.2022.02.015
9. Tryggestad EJ, Wei L, Pepin MD, Hallemeier CL, Sio TT. Managing treatment related
uncertainties in proton beam radiotherapy for gastrointestinal cancers. J Gastrointest
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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
11. Liu W, Schild SE, Chang JY, Keole S, Wong W, Bues M. Exploratory study of 4D
versus 3D robust optimization in intensity modulated proton therapy for lung cancer. Int J
Radiat Oncol Biol Phys. 2015;(95):523-533. http://doi.org/10.1016/j.ijrobp.2015.11.002
12. Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG oncology RTOG 0617:
standard- versus high-dose chemoradiotherapy with or without cetuximab for
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http://doi.org/10.1200/JCO.19.01162
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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 represents a CTV volume delineated by the physician. The magenta
color along the lung and tissue interface represents the HU optimization structure created for this
study, given an HU override value of either -400, -200, or 0.
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Figure 2. Values obtained for statistical analysis without and with an HU optimization structure
for target plan robustness evaluation are shown above for one patient within our research
population. Original plans are shown in a dark color (blue representing no override, green
representing an override using HU -400, yellow representing an override using HU -200, and red
representing an override using HU 0). 5 associated verification plans are shown in a lighter color
following their corresponding original plan. In the first complete plan without an HU override
(blue), the final verification scan (black) would not have met our target robustness evaluation
criteria of D95% ≥ 100% ± 5% as it resulted in 94.2% coverage, below the lower 95% threshold.
On the other hand, each associated plan created with an HU optimization structure would have
maintained robustness ± 5% throughout the full course of treatment.
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Figure 3. 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 dark blue.
Original plans using an HU optimization structure with an override value of –400 are shown in
green, -200 are shown in yellow, and 0 are shown in red.
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Figure 4. 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 light blue. Verification plans using an HU optimization structure with
an override value of –400 are shown in light green, -200 are shown in light yellow, and 0 are
shown in light red.