Variations in linear energy transfer within clinical proton therapy fields and the potential for biological treatment planning

Abstract

Purpose: To calculate the linear energy transfer (LET) distributions in patients undergoing proton therapy. These distributions can be used to identify areas of elevated or diminished biological effect. The location of such areas might be influenced in intensity-modulated proton therapy (IMPT) optimization.

Methods and materials: Because Monte Carlo studies to investigate the LET distribution in patients have not been undertaken so far, the code is first validated with simulations in water. The code was used in five patients, for each of them three planning and delivery techniques were simulated: passive scattering, three-dimensional modulation IMPT (3D-IMPT), and distal edge tracking IMPT (DET-IMPT).

Results: The inclusion of secondary particles led to significant differences compared with analytical techniques. In addition, passive scattering and 3D-IMPT led to largely comparable LET distributions, whereas the DET-IMPT plans resulted in considerably increased LET values in normal tissues and critical structures. In the brainstem, dose-averaged LET values exceeding 5 keV/μm were observed in areas with significant dose (>70% of prescribed dose). In noncritical normal tissues, even values >8 keV/μm occurred.

Conclusion: This work demonstrates that active scanning offers the possibility of influencing the distribution of dose-averaged LET (i.e., the biological effect) without significantly altering the distribution of physical dose. On the basis of this finding, we propose a method to alter deliberately the LET distribution of a treatment plan in such a manner that the LET is maximized within certain target areas and minimized in normal tissues, while maintaining the prescribed target dose and dose constraints for organs at risk.

Fig. 1

Representative slice of the 3D-IMPT (upper part) and DET-IMPT (lower part) plans for patient I, calculated with Monte Carlo. Contours for GTV and brainstem are shown in blue and green, respectively. Left: dose in percent of prescribed dose, entrance direction of the two co-planar fields indicated by white arrows. Right: LET_d distribution in keV/μm. Dose and LET_d values below 0.1% of maximum values have been made transparent.

Fig. 2

LET_d-volume histograms (LVHs) of GTV, brainstem and pituitary gland for patient I. The figure at the lower right visualizes the differences between the LET_d distributions, i.e. [LET_d (3D-IMPT) − LET_d (DET-IMPT)]. The red areas indicate that the 3D modulation plan has higher LET_d values, while the blue areas shows that the DET-IMPT plan causes a higher LET_d. The scale plots the difference in LET_d in keV/μm.

Fig. 3

Representative slice of the 3D-IMPT (upper part) and DET-IMPT (lower part) plans for patient II. Left: dose in percent of prescribed dose. Right: LET_d distribution in keV/μm. Dose and LET_d values below 0.1% of maximum values have been made transparent. Contours for GTV, retinas and chiasm are shown in red, green and yellow, respectively.

Fig. 4

LVHs of GTV, right retina and chiasm for patient II.

Fig. 5

Representative slice showing the LET_d distribution of the 3D-IMPT (left) and DET-IMPT (right) plan for patient III (color bar in units of keV/μm). Values below 0.1% of maximum have been made transparent. The target is contoured in white, entrance direction of beams indicated by white arrows.

Fig. 6

Schematic illustration to show which beam spots would be available to the optimization routine for two opposing fields and one lateral field in the presence of two critical structures left and right of the target.