Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy

Abstract

Background: Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LET_d) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LET_d was reported.

Purpose: The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LET_d in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LET_d optimization functions of a commercial treatment planning system (TPS).

Methods: Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than $250{\mathrm{cm}}^3$ were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was $D_{\mathrm{RBE},50\%}=73.6\mathrm{Gy}$ in 16 fractions (nine to low dose and seven to high dose planning target volume). No LET_d optimization was performed in the reference plans, while LET_d optimized plans used the minimum LET_d (L_min) optimization function in RayStation 2023B. Three different L_min values were investigated and specified for the seven boost fractions: $L_{\min }=60\mathrm{keV}/\mu m$ , $L_{\min }=80\mathrm{keV}/\mu m$ and $L_{\min }=100\mathrm{keV}/\mu m$ . To compare the LET_d optimized against reference plans, LET_d and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( $\pm 3.5\%$ range uncertainty and $\pm 3\mathrm{mm}$ setup uncertainty along the main three axes).

Results: The optimization method with $L_{\min }=60\mathrm{keV}/\mu m$ resulted in an optimal LET_d distribution with an average increase of ${\mathrm{LET}}_{d,98\%}$ (and ${\mathrm{LET}}_{d,50\%}$ ) in the CTV-HD by $8.9\pm 1.5\mathrm{keV}/\mu m$ ( $27\%$ ) (and $6.9\pm 1.3\mathrm{keV}/\mu m$ ( $17\%$ )), without significant difference in the RBE-weighted dose. By allowing $\pm 5\%$ over- and under-dosage in the target, the ${\mathrm{LET}}_{d,98\%}$ (and ${\mathrm{LET}}_{d,50\%}$ ) can be increased by $11.3\pm 1.2\mathrm{keV}/\mu m$ ( $34\%$ ) (and $11.7\pm 3.4\mathrm{keV}/\mu m$ ( $29\%$ )), using the optimization parameters $L_{\min }=80\mathrm{keV}/\mu m$ . The pass rate for the OAR goals in the LET_d optimized plans was in the same level as the reference plans. LET_d optimization lead to less robust plans compared to reference plans.

Conclusions: Compared to conventionally optimized treatment plans, the LET_d in the target was increased while maintaining the RBE-weighted dose using TPS LET_d optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects during treatment.

Keywords: LET optimization; LET painting; carbon ion radiotherapy; carbon ion treatment planning.