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.