Joint Optimization of Photon-Carbon Ion Treatments for Glioblastoma

Carbon ions are radiobiologically more effective than photons and are beneficial for treating radioresistant gross tumor volumes (GTV). However, owing to a reduced fractionation effect, they may be disadvantageous for treating infiltrative tumors, in which healthy tissue inside the clinical target volume (CTV) must be protected through fractionation. This work addresses the question: What is the ideal combined photon-carbon ion fluence distribution for treating infiltrative tumors given a specific fraction allocation between photons and carbon ions?

We present a method to simultaneously optimize sequentially delivered intensity modulated photon (IMRT) and carbon ion (CIRT) treatments based on cumulative biological effect, incorporating both the variable relative biological effect of carbon ions and the fractionation effect within the linear quadratic model. The method is demonstrated for 6 glioblastoma patients in comparison with the current clinical standard of independently optimized CIRT-IMRT plans.

Compared with the reference plan, joint optimization strategies yield inhomogeneous photon and carbon ion dose distributions that cumulatively deliver a homogeneous biological effect distribution. In the optimal distributions, the dose to CTV is mostly delivered by photons and carbon ions are restricted to the GTV with variations depending on tumor size and location. Improvements in conformity of high-dose regions are reflected by a mean EQD2 reduction of 3.29 ± 1.22 Gy in a dose fall-off margin around the CTV. Carbon ions may deliver higher doses to the center of the GTV, and photon contributions are increased at interfaces with CTV and critical structures. This results in a mean EQD2 reduction of 8.3 ± 2.28 Gy, in which the brain stem abuts the target volumes.

We have developed a biophysical model to optimize combined photon-carbon ion treatments. For 6 glioblastoma patient cases, we show that our approach results in a more targeted application of carbon ions that (1) reduces dose in normal tissues within the target volume, which can only be protected through fractionation; and (2) boosts central target volume regions to reduce integral dose. Joint optimization of IMRT-CIRT treatments enable the exploration of a new spectrum of plans that can better address physical and radiobiological treatment planning challenges.