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Dependence of LET-Enhancement On Patient-Specific Anatomy in Intensity Modulated Proton Therapy Treatment Planning for Rectal Cancer

J Rivera1*, K Gergelis1, R Mutter1, H Wan Chan Tseung1, C Hallemeier1, N Remmes1, M Herman1, J Ma1, (1) Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA

Presentations

MO-H345-IePD-F4-5 (Monday, 7/11/2022) 3:45 PM - 4:15 PM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 4

Purpose: Linear energy transfer (LET) is closely related to radiobiological effects in proton therapy and may be leveraged as a key planning parameter in intensity modulated proton therapy (IMPT) to escalate biological dose (BD). Focusing higher LET within gross tumor volume (GTV) while minimizing it in organs-at-risk may result in superior tumor control and normal-tissue sparing compared to standard IMPT plans. Hence, there is strong interest to perform clinical studies with LET-enhancement. We previously demonstrated BD-escalation feasibility using an in-house Monte Carlo–based inverse-planning optimizer for enhancing LET. We hypothesize patient anatomy influences LET enhancement thereby limiting resulting BD. This study systematically evaluates effects of patient-specific anatomical characteristics on GTV-LET and resulting plan quality for LET-optimized and standard IMPT plans.

Methods: Single field optimization (SFO) and Monte Carlo-based optimization were used to create standard and LET-enhanced IMPT plans using two equally-weighted posterior-oblique fields. Prescription dose included two target volumes (CTV=2500cGy, GTV=2800cGy). LET-enhanced plans were optimized to achieve enhanced GTV-BD while meeting the same OAR constraints. Simple and multivariate hierarchical linear regression analyses were utilized to assess the influence of select anatomical parameters on LET-enhancement/plan quality and Pearson Correlation matrix determined cross-correlations between parameter pairs. Relevant metrics included target location, volume, shape, laterality, among others.

Results: LET/plan quality vs anatomical parameters plots demonstrated GTV-LET in standard IMPT SFO plans was inversely associated with GTV-distance-to-CTV, while LET-enhanced plans did not share this dependence. In LET-enhanced plans, GTVs with higher LET were achieved in narrower volumes suggesting GTV shape may influence LET. GTV-LET enhancement was inversely associated with plan Robustness.

Conclusion: LET-guided IMPT planning for rectal cancer GTV-BD escalation is feasible. Patient-specific anatomical characteristics may limit LET-enhancement and resulting BDs. Study results will be used to build quantitative nomograms between target LET value/plan quality and key anatomical metrics, which will guide clinical LET-enhanced planning.

Keywords

LET, Optimization, Protons

Taxonomy

TH- External Beam- Particle/high LET therapy: Proton therapy – treatment planning/virtual clinical studies

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