Working Title

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

proton treatment
Problem Statement
The problem is that the verification process for patients receiving phase-gated proton treatment
requires the creation of a new phase-gated average scan which is time consuming, requires
additional clinical resources, and is incompatible with current software used for automatic
verification planning.
Purpose Statement
The purpose of this study is to compare target coverage (V95%) reported on phase-gated average
verification plans to target coverage on single-phase verification plans to ensure that the results
are within 5% to ensure clinical acceptability.
Hypotheses Statements or Research Questions
H1A: The first research hypothesis (H1) is that a single-phase verification plan will result in
reported CTV coverage (V95%) that is within 5% of the reported CTV coverage for a phase-
gated average verification plan for patients receiving phase-gated proton treatment.
H10: The first null hypothesis (H10) is that a single-phase verification plan will not result in
reported CTV coverage (V95%) that is within 5% of the reported CTV coverage for a phase-
gated average verification plan for patients receiving phase-gated proton treatment.
Summary
The use of intensity modulated proton therapy (IMPT) has become common in the
treatment of chest and abdominal treatment sites due to the advantages protons have to offer in
comparison to conventional radiotherapy. Due to the nature of proton interactions and their finite
range, proton therapy offers the benefit of sparing healthy organs along with a more conformal
dose distribution.1 Finite proton range increases dose conformality but is sensitive to changes in
patient anatomy.2 Variations in patient setup and changes in anatomy may change dose
distributions. This affects target coverage and sparing of organs at risk.3 These metrics are often
utilized to determine the necessity of plan adaptation.

Due to these plan uncertainties, routine verification scanning is needed to ensure safe and
effective treatments when utilizing IMPT. Regular verifications can be used to assess changes in
patient anatomy and subsequent effects on treatment plan quality and consistency. Verification
CT scans are used to evaluate that the current dose distribution has not changed in an
unacceptable manner from the original treatment plan.4 Modifications in treatment plans
throughout the course of treatment delivery are used to account for changes in target volumes,
normal structures, and patient contours.5 A study conducted by Deiter et al3 did not find a
correlation between the necessity of replanning and various dosimetric variables. Replanning is
also often required late in treatment (beyond 4 weeks).2 This demonstrates the need for an
efficient and routine verification CT scanning process as well as replanning when necessary to
ensure plan quality.

Chest and abdominal treatment sites often suffer from target motion due to normal
breathing and require the use of a 4D phase gated treatment technique to mitigate motion effects
on treatment. Due to its complexity, IMPT has increased sensitivity to factors that impact plan
quality including breathing motion management.1 Tumor motion of the esophagus, pancreas, and
liver is between 3-20 mm on average resulting in the need for motion management during
treatment delivery.1 Motion interplay can also greatly affect the quality of treatment delivery
during spot-scanning proton therapy.6 4DCT is the standard for motion evaluation and treatment
planning for mobile targets. 4DCT imaging results in 10 separate 3D CT volumes, each
representing a portion of the breathing cycle. The goal of respiratory gating is to treat only
during latent portion of respiration near expiration. This is more consistent and reproducible. The
treatment plan is generated on a 4DCT that includes only these phases of respiration.1

Thoracic and abdominal treatment sites requiring 4D phase gated treatment often require
replanning throughout the course of treatment. A study conducted by Hu et al2 found that H&N
and lung/chest sites require the largest amount of re-planning. For patients with esophageal
cancer treated with IMPT every other week verification scans should be considered.7 Replanning
is required for about 25% of cases in motion management disease sites, therefore treatment sites
requiring motion management require plan verification typically weekly.6 In an evaluation of
replanning frequency by Mundy et al,8 the replan rate for esophagus sites was 17%, and liver-
pancreas-adrenal was 22% of patients. Verification scanning is required for GI sites treated with
IMPT. 4D Verifications require extra time and clinical resources. This is due to the fact that the
treatment plan was created on a subset of 4D images, the phase gated average must be recreated
each time a verification is acquired.
 The verification process requires extensive clinical resources and disrupts clinical
workflow. This includes CT scanner time and clinical personnel including therapists, physicists,
medical dosimetrists, and physicians. Verification CT scans can be performed with an in-room
CT-on-rails system or routine CT simulator and are acquired utilizing the same scan parameters.4
Verification planning involves registering the verification scan to the original planning scan and
calculating dose on the current scan. Both rigid and deformable registrations are used to transfer
structures to the verification scan.2 Target coverage and OAR DVH parameters are evaluated,
and a physician’s clinical judgement ultimately determines the need for a replan.4 The
verification process can be time consuming and labor intensive.

In addition to utility in verification scanning, in room CT-on-rails scanning offers an

opportunity to employ online adaptive therapy in the context of IMPT. Adaptive radiation
therapy (ART) involves monitoring the delivered dose throughout the course of treatment and
modifying the treatment plan as needed to improve the clinical outcome of treatment by
maximizing the dose to the target and minimizing the normal tissue dosage.5 Adaptive proton
therapy includes both online, performed at the time of treatment, and offline, performed between
treatments.2 Online ART is best for suited for treatment areas that have anticipated need for
adaption, this includes intra-abdominal sites due to intrafraction changes in locations of OAR.5

Efficient workflows are necessary when considering the implementation of an on-line

adaptive imaging protocol. Adaptive radiation therapy is complex and labor intensive, including
imaging, assessment, replanning, and quality assurance.5 Decreased efficiency can result in
targeting inaccuracies.1 Changes can occur between the time of imaging and beam delivery. 4D
phase-gated treatments take additional time that may limit the accuracy of treatment. Phase gated
treatments have an efficiency cost including longer treatment times, due to repainting and
effective duty cycle.6 The effective duty cycle is often less than planned/ideal due to variable
breathing, synchrotron behaviors, and plan complexity.6 Long treatment times reduce
efficiencies, lead to patient discomfort and possible patient motion during treatment decreasing
quality of treatment delivery.

4D Verification scans are not compatible with auto verification software needed for
online adaptive therapy. Online ART is performed in the treatment room immediately prior to
treatment delivery. This process needs to be efficient and requires specialized tools. A lean
workflow approach is desirable.5 This research would compare verification on a single phase of a
4D image set with a verification on the current standard of the phase gated average image set. If
found to be equivalent in terms of dose statistics and clinical acceptability regarding replan
judgment, this would allow for a more efficient offline verification process and allow for
potential online adaptive therapy for patients treated with 4D phase gated IMPT.

Adaptive proton planning requires quick and efficient AI contouring and verification
software. The problem is that the verification process for patients receiving phase-gated proton
treatment requires the creation of a new phase-gated average scan which is time-consuming,
requires additional clinical resources, and is incompatible with current software used for
automatic verification planning. The purpose of this study is to compare target coverage (V95%)
reported on phase-gated average verification plans to target coverage on single-phase verification
plans to ensure that the results are within 5% to ensure clinical acceptability. This study would
allow for increased efficiency in verification planning for phase gated proton treatments as well
as create compatibility with automatic verification planning software which will be essential for
future adaptive planning capabilities. Researchers tested the hypothesis that a single-phase
verification plan will result in reported CTV coverage (V95%) that is within 5% of the reported
CTV coverage for a phase-gated average verification plan for patients receiving phase-gated
proton treatment.

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Fakhraei S, Johnson JEJ, Tryggestad EJ, et al. Retrospective Analysis of Replan Frequency
and Causes in Esophageal Cancer Patients Treated with Spot Scanned Proton Therapy. Int J of
Rad Oncol, Biol, Phys. 2022;114(3):158-159.
8. Mundy D, Harper R, Deiter N. Analysis of spot scanning proton verification scan and re-plan
frequency. Med Phys. 2019;46(6):250.