Group 1: Research Proposal (Draft 4 Updated)

Ma Kathreen Hazel Rosales, Mark Brennan, and Jenna Lombardo

Working Title
Enhancing Dosimetric Outcomes Using Ethos Online Adaptive Radiation Therapy with
RapidPlan for Prostate Bed and Lymph Node Irradiation

Problem Statement
The problem is excess dose to proximal OAR (rectum and bladder) when using ETHOS
adaptive radiotherapy software.

Purpose Statement
The purpose of this study is to assess whether adding RapidPlan to Ethos adaptive
planning can improve OAR sparing.

Hypotheses Statements or Research Questions

By conducting a head-to-head comparison of treatment plans using previously
administered on-couch adaptive radiation therapy (oART) sessions within the Ethos platform, we
plan to analyze five treatment fractions from five distinct patients (a total of 25 fractions) who
underwent oART for treatment to the prostate bed and lymph nodes.
Leveraging the existing patient anatomy from these clinically treated sessions, our
objective is to determine whether integrating two different RapidPlan models can consistently
improve dosimetric outcomes compared to relying solely on a novel, priority-based optimizer.
We will assess the efficacy of each RapidPlan model in producing consistent results and identify
how their inclusion can improve treatment outcomes.
H1A: The first research hypothesis (H1) is that adding RapidPlan to Ethos Adapting Planning
will reduce the mean dose to the rectum by ≥ 5% while maintaining PTV coverage.
H10: The first null hypothesis (H10) is that adding RapidPlan to Ethos Adapting Planning will not
reduce the mean dose to the rectum by ≥ 5% while maintaining PTV coverage.
H2A: The second research hypothesis (H21) is that Adding RapidPlan to Ethos Adapting Planning
will reduce the maximum dose to the rectum by ≥ 5% while maintaining PTV coverage.
H20: The second null hypothesis (H20) is that Adding RapidPlan to Ethos Adapting Planning will
not reduce the maximum dose by ≥ 5% to the rectum while maintaining PTV coverage.
H3A: The third research hypothesis (H31) is that Adding RapidPlan to Ethos Adapting Planning
will reduce the mean dose to the bladder by ≥ 5% while maintaining PTV coverage.
H30: The third null hypothesis (H30) is that Adding RapidPlan to Ethos Adapting Planning will
not reduce the mean dose by ≥ 5% to the bladder while maintaining PTV coverage.
H4A: The fourth research hypothesis (H41) is that Adding RapidPlan to Ethos Adapting Planning
will reduce the maximum dose to the bladder by ≥ 5% while maintaining PTV coverage.
H40: The fourth null hypothesis (H40) is that Adding RapidPlan to Ethos Adapting Planning will
not reduce the maximum dose to the bladder by ≥ 5% while maintaining PTV coverage.

Literature Review Summary

Prostate cancer patients often require tailored, complex treatment planning techniques to
manage or control disease without compromising quality of life due to acute and late toxicities.
Additionally, treatment techniques such as IMRT, which offers conformal radiation delivery
with modulated intensity beams, and SBRT (Stereotactic Body Radiation Therapy), which
delivers high doses in fewer sessions, enhance convenience and potentially improve tumor
control.1 Prostate cancer patients who receive greater doses of organs at risk (OAR) such the
rectum and bladder experience increased acute toxicities such as proctitis and rectal bleeding. 2
However, both IMRT and SBRT plans frequently result in acute grade 2 or higher
gastrointestinal (GI) and genitourinary (GU) toxicity due to daily anatomical changes and high
rectum and bladder dose constraints (V70Gy<15% for IMRT, V40Gy<15% for SBRT).2
Moreover, the introduction of online adaptive radiotherapy (oART), as used by Varian
Ethos, has revolutionized prostate cancer treatments. OART provides precise targeting and
higher target doses while minimizing exposure to healthy tissues, enhancing treatment outcomes
for those cancer patients.5 Byrne et al. (2022) and Byrne et al. (2023) present early results of
intrafraction motion and margin assessment for Ethos online adaptive radiotherapy treatments,
respectively. These studies highlight the potential of Ethos in contouring accuracy, treatment
plan quality, and reduction of toxicities. Along with the contributions by Moazzezi et al. (2021)
and Pokharel et al. (2022), these studies collectively underscore the promising role of Ethos in
enhancing treatment efficacy and precision while minimizing adverse effects, thus representing a
significant stride in radiotherapy for prostate cancer.
However, there are a limited number of publications on the Intelligent Optimization
Engine. Recently, UTSW published their experience on using both an in-house and
commercially available knowledge-based planning tool (Varian RapidPlan) in concert with the
IOE.9 They demonstrated that for head and neck patients, incorporating RapidPlan improved
dosimetric goals relative to not using RapidPlan, and the in-house models outperformed both
RapidPlan and the IOE alone. This was conducted once weekly oART in the head and neck. In
this study, we propose to follow a similar procedure for our pelvic cohort.9
The study will provide valuable insights into the planning efficiency and dosimetric
characteristics of Varian Ethos’ adaptive plans compared to those utilizing RapidPlan model.
These findings will offer guidance for clinicians in selecting the most appropriate radiation
therapy technique based on individual patient characteristics and treatment goals by evaluating
the extent of rectal and bladder toxicities resulting from each treatment method while reducing
the planning time (reduced treatment table time). Thus, the evolution of radiation therapy
techniques from IMRT and SBRT to adaptive planning with Ethos illustrates the ongoing efforts
to refine prostate cancer treatment. By leveraging Ethos' capabilities to adapt to variations in
anatomy for each treatment, there is enormous potential to reduce unnecessary dose to organs at
risk and the incidence of acute GI and GU toxicities. This is a crucial step toward optimizing
radiation therapy for prostate cancer, emphasizing the importance of individualized treatment
approaches that prioritize both efficacy and patient quality of life.
Radiation therapy for prostate cancer patients can still cause side effects due to excess
doses to organs at risk (OAR), including the bladder and rectum. To lessen toxicities, it is crucial
to eliminate unnecessary dosages to these OAR. The problem is excess dose to proximal OAR
when using ETHOS adaptive radiotherapy software without using the RapidPlan model. The
study's purpose is to determine whether Ethos adaptive planning utilizing the RapidPlan model,
can significantly reduce dose to the rectum and bladder, effectively reducing the risk of toxicity,
as well as reduced the dosimetric uncertainties for on-couch adaptive radiation therapy (both for
the initial reference plan and for plans generated from daily anatomy). By evaluating the
dosimetric impacts of Ethos adaptive plans using RapidPlan in comparison to adaptive plans
alone, this research posits that Ethos adaptive planning with RapidPlan can significantly mitigate
OAR doses in prostate cancer radiotherapy, addressing the hypotheses that RapidPlan will
reduce dose to all proximal OAR (H1A), decrease the mean dose to the rectum (H2A) and
bladder (H3A), as well as the maximum doses to these critical structures (H4A and H5A).
References
1. Samir F, Meaz TM, Hussiny FA, et al. Analytical dosimetric study of intensity-modulated
radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for prostate cancer. J
Cancer Res Clin Oncol. 2023;149(9):6239-6246. doi:10.1007/s00432-023-04586-5
2. Ozkan EE, Ozseven A, Cerkesli ZAK. Evaluating the predictive value of quantec rectum
tolerance dose suggestions on acute rectal toxicity in prostate carcinoma patients treated with
IMRT. Rep Pract Oncol Radiother. 2020;25(1):50-54. doi: 10.1016/j.rpor.2019.12.002
3. Byrne M, Archibald-Heeren B, Hu Y, et al. Varian ethos online adaptive radiotherapy for
prostate cancer: Early results of contouring accuracy, treatment plan quality, and treatment
time. J Appl Clin Med Phys. 2022;23(1): e13479. doi:10.1002/acm2.13479
4. Byrne M, Teh AYM, Archibald-Heeren B, et al. Intrafraction Motion and Margin
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planning system for radiotherapy of anal, rectal, and prostate cancer. Tech Innov Patient
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optimization-engine (IOE) performance for ethos head-and-neck (HN) plan generation. J
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