J Rivera*, J Ma, K Gergelis, R Mutter, H Wan Chan Tseung, C Hallemeier, N Remmes, M Herman, Mayo Clinic, Rochester, MN

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  J Rivera

TU-IePD-TRACK 5-6 (Tuesday, 7/27/2021) 12:30 PM - 1:00 PM [Eastern Time (GMT-4)]

Purpose: Intensity modulated proton beam therapy (IMPT) affords exquisite geometric control of dose deposition in targets and enables improved sparing of normal tissues; however, critical, dose-limiting structures may prevent the delivery of curative radiation doses. We previously demonstrated the feasibility of using an in-house Monte Carlo–based inverse planning optimizer to capitalize on a convergence of Bragg peaks to enhance the linear energy transfer (LET) in a given volume. The resulting increase in biological dose (BD) achievable may provide superior anti-tumor effects for treating otherwise highly radio-resistant tumors. This planning study systematically evaluates various parameters in the optimizer in an effort to escalate high-LET within targets while limiting deposition of high-LET within organs-at-risk (OAR). We hypothesize modest LET escalation in rectal plan GTVs may be leveraged to enhance BD while meeting OAR constraints.

Methods: Standard and LET-enhanced IMPT plans are created for 10 resectable (T2-T3) rectal cancer patients. Patients are planned with Eclipse and Monte Carlo-based optimization to the same prescription dose, including two target volumes (CTV 2500cGy, GTV 2800cGy) and two equally-weighted posterior-oblique fields. Multivariate generalized linear models are used to assess the influence of planning and optimization parameters on LET-enhancement, physical, and biological dose. Relevant metrics include CTV/GTV coverage reproducibility with changes in internal organ motion, rectal gas filling, patient positioning, and tissue density inhomogeneities.

Results: Dose-volume histogram (DVH)-analyses reveal LET-guided plans achieved comparable CTV physical dose homogeneity and OAR sparing compared to standard IMPT plans. LET-guided plans also achieved significant LET and BD enhancement in GTVs. However, robustness analyses of plans cast onto verification CTs indicate LET-enhancement in GTV may inversely correlate with plan Robustness for select optimization parameters.

Conclusion: LET-guided IMPT planning for rectal cancer GTV biological dose escalation is feasible. Although tradeoffs exist between optimization parameters, LET-enhanced rectal treatments may allow for enhanced therapeutic windows.

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