Introducing Proton Track-End Objectives in Intensity Modulated Proton Therapy Optimization to Reduce Linear Energy...

We propose the use of proton track-end objectives in intensity modulated proton therapy (IMPT) optimization to reduce the linear energy transfer (LET) and the relative biological effectiveness (RBE) in critical structures.

IMPT plans were generated for 3 intracranial patient cases (1.8 Gy (RBE) in 30 fractions) and 3 head-and-neck patient cases (2 Gy (RBE) in 35 fractions), assuming a constant RBE of 1.1. Two plans were generated for each patient: (1) physical dose objectives only (DOSEopt) and (2) same dose objectives as the DOSEopt plan, with additional proton track-end objectives (TEopt). The track-end objectives penalized protons stopping in the risk volume of choice. Dose evaluations were made using a RBE of 1.1 and the LET-dependent Wedenberg RBE model, together with estimates of normal tissue complication probabilities (NTCPs). In addition, the distributions of proton track-ends and dose-average LET (LET_d) were analyzed.

The TEopt plans reduced the mean LET_d in the critical structures studied by an average of 37% and increased the mean LET_d in the primary clinical target volume (CTV) by an average of 23%. This was achieved through a redistribution of the proton track-ends, concurrently keeping the physical dose distribution virtually unchanged compared to the DOSEopt plans. This resulted in substantial RBE-weighted dose (D_RBE) reductions, allowing the TEopt plans to meet all clinical goals for both RBE models and reduce the NTCPs by 0 to 19 percentage points compared to the DOSEopt plans, assuming the Wedenberg RBE model. The DOSEopt plans met all clinical goals assuming a RBE of 1.1 but failed 10 of 19 normal tissue goals assuming the Wedenberg RBE model.

Proton track-end objectives allow for LET_d reductions in critical structures without compromising the physical target dose. This approach permits the lowering of D_RBE and NTCP in critical structures, independent of the variable RBE model used, and it could be introduced in clinical practice without changing current protocols based on the constant RBE of 1.1.