Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer

Abstract

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution.

Methods and materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET.

Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives.

Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.

Figure 1

Plan comparison for the atypical meningioma (case 1): a) contours for target volume (red), GTV (brown), brainstem (green), optic structures and pituitary gland (yellow); c and e) physical dose and LETxD for the reference plan; d and f) physical dose and LETxD for the reoptimized plan; b) difference in physical dose, positive values indicate higher doses in the reference plan.

Figure 2

DVH comparison for the atypical meningioma (case 1) between reference plan (solid lines) and reoptimized plan (dashed lines). (a) physical dose DVHs, showing identical target coverage for both plans; (b) DVHs evaluated for LETxD (scaled with c = 0.04 μm/keV). In the LETxD DVH of the brainstem, voxels that receive less than 10 Gy physical dose in the reference plan were removed for better visualization. The black lines correspond to all normal tissue voxels in a 1 cm margin around the target volume.

Figure 3

Plan comparison for the ependymoma (case 2).

Figure 4

Plan comparison for the base-of-skull chordoma (case 3).

Figure 5

Difference in physical dose (Gy) between the dose-escalated plan and Figure 1e, i.e. the figure shows the additional physical dose on top of 50 Gy, which can be delivered to the GTV without worsening any normal tissue dose objective. The corresponding LETxD distribution is shown in the supplementary materials (Appendix E.2).