Kristen Dezell

Brittni McKane

Carissa Rivinius

Group 3: Research Proposal Document

Working Title:

Increasing inter-fraction target robustness in proton lung radiotherapy using a planning

optimization structure.

Problem Statement:

The problem is maintaining robust target coverage between the target volume and lung overlap
region due to inter-fraction tumor and anatomy changes.

Purpose Statement:

The purpose of this study is 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.

Hypothesis Statements or Research Questions:

H1A: The first research hypothesis (H1) is that using an HU override value of –400 to the
optimization structure will increase robustness of proton lung planning and maintain inter-
fraction CTV coverage of D95% ≥ 100%.

H10: The first research null hypothesis (H10) is using an HU override value of –400 to the
optimization structure will not increase robustness of proton lung planning and maintain inter-
fraction CTV coverage of D95% ≥ 100%.
H2A: The second research hypothesis (H2) is using an HU override value of –200 to the
optimization structure will increase robustness of proton lung planning and maintain inter-
fraction CTV coverage of D95% ≥ 100%.

H20: The second research hypothesis (H20) is using an HU override value of –200 to the
optimization structure will not increase robustness of proton lung planning and maintain inter-
fraction CTV coverage of D95% ≥ 100%.

H3A: The third research hypothesis (H3) is using an HU override value of 0 to the optimization
structure will increase robustness of proton lung planning and maintain inter-fraction CTV
coverage of D95% ≥ 100%.

H30: The third research hypothesis (H30) is using an HU override value of 0 to the optimization
structure will not increase robustness of proton lung planning and maintain inter-fraction CTV
coverage of D95% ≥ 100%.

Literature Review:

Traditionally, photon beam intensity modulated radiation therapy (IMRT) was utilized
for the treatment of lung cancer. As advancements have been made, proton therapy has become
an enticing modality to utilize due to the relative stopping power and resulting decreased dose to
nearby healthy tissue.1,2 There have been challenges associated with this technique from lacking
research for QA phantoms with heterogeneity features to the ability to account for respiratory
motion.3 Proton beam planning has improved the ability to spare organs at risk (OAR) and
maintain target coverage due to the Bragg peak.2 However, tumors treated in the thoracic region
struggle to maintain robustness to the target volume along the target volume and lung overlap
throughout the entirety of a patients' treatment plan. This can be caused by several factors
including tumor motion and its effect on the Bragg peak, tissue heterogeneities, shrinking or
growth of the tumor volume throughout treatment, or the algorithm utilized for planning (plan
robustness).3,4 It is essential to maintain target coverage throughout a patient's course of radiation
to gain the best clinical outcome while sparing nearby OAR volumes.

Historically, until around five or so years ago, the pencil beam algorithm has been the
main algorithm commercially available and utilized.3 Although, there are a variety of
complexities in the thoracic region which impose challenges in predicting accurate dose
distribution when using the pencil beam scanning (PBS) proton therapy algorithm, especially
under the impact of organ or tumor motion.1,5This makes the dose calculation accuracy in
heterogeneous tissues a concern. It is well known that proton radiation in the lung parenchyma
will travel further due to low density tissue.1 Utilizing the Monte Carlo algorithm has made
significant improvements in dose accuracy in the thoracic region when used with 4DCT
planning.5Han et al.3 reported that using the Monte Carlo algorithm over PBS in areas when an
air gap is wider than 10cm produced a 3-11% dose difference with PBS and was only 2%
different for the Monte Carlo algorithm. As there have been technological advancements it has
been found that using the Monte Carlo algorithm gives a higher accuracy for dose prediction in
inhomogeneous media.3

Enhancements in proton planning have provided opportunities to improve plan

robustness. Robustness builds into a proton plan to work against geometric uncertainty or more
simply ensures that range or setup errors do not result in increased dose to OARs or under
coverage of the target.6 In the past, the capability to monitor tumor motion for radiation planning
was nonexistent. As advancements have been made, CT scanners now have the ability to perform
a 4D scan monitoring respiration and tumor motion, which is critical in the thoracic region. This
aids physicians in targeting the tumor volume while sparing more healthy tissue and OAR
volumes nearby. Mobile target volumes can cause something called an interplay effect, where
the small spots of the proton pencil beam can miss the target due to intra-gate motion and
therefore cause less dosimetric certainty. To combat this effect, layer-based repainting combined
with 4D motion analysis can drastically improve overall plan robustness.5,7,8

Knowing these challenges we face in proton planning, and the miniscule past research
regarding Hounsfield Unit (HU) override of the entire internal target volume (ITV) in proton
lung planning9, we found that there is a need for further research on HU overrides in the thoracic
region for proton plan robustness. Tryggestad et al.10 discusses the gain in dosimetric robustness
when utilizing HU overrides in air-filled cavities with relative values from nearby structures.
Implementing additional CT scans during treatment to verify dosimetric robustness was
considered in this study, as well as evaluating the potential for replanning.10 Previous research
has utilized HU overrides to an entire structure such as the planning target volume (PTV) or
internal target volume (ITV), whereas our study focuses specifically on the target volume and
lung overlap surrounding the tumor volume within the CTV but not as a whole. This becomes
essential as the studies by Botas et al.5 and Wei et al.11 resulted in a significant increase in plan
robustness and target coverage by overriding the entire ITV, but the surrounding OAR structures
also received a greater dose.

As radiation continues to play a vital role in the treatment of lung cancer for many
patients, plan robustness along the target volume and lung overlap throughout treatment needs to
be addressed. The proton modality is increasingly important as protons are expected to be
treating over 300,000 patients by the year 2030 compared to 190,000 in 2018.3 The problem is
maintaining robust target coverage between the target volume and lung overlap region due to
inter-fraction tumor and anatomy changes. The use of a specific HU override structure could
potentially increase coverage to the target volume while sparing dose to the OAR volumes, but
there remains to be little literature evaluating this topic. The purpose of this study is 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 inter-fraction target coverage. Utilizing
the nonlinear universal proton optimizer (NUPO) and a Monte Carlo second check, 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% without increasing
dose to nearby OARs.
 References
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