Session Item

Carbon ions show higher RBE and reduced fractionation effect near the Bragg peak, which has advantages for the treatment of radioresistant gross tumor volumes (GTV) However, carbon ions face limitations for treating infiltrative disease when normal tissues inside the clinical target volume (CTV) must be protected through fractionation. These characteristics gave rise to combined photon-carbon ion treatments in which carbon ions give a boost to the GTV while photons irradiate the CTV. Here, we investigate a novel strategy to jointly optimize both photon and carbon ion fractions in order to determine the optimal combination of both modalities for Glioblastoma (GBM) cases.

Joint optimization of pencil beam intensities for carbon ions and of fluence maps for photons is performed based on the cumulative biological effect (BE) of the two modalities, i.e., the negative log of the survival fraction from the linear quadratic cell survival model. The carbon ion effect is calculated based on the Local Effect Model; constant radiobiological parameters alpha and beta are assumed for photons. Dose prescriptions and normal tissue constraints are adopted from the CLEOPATRA-GBM trial, i.e., 25 photon fractions deliver 50Gy to the CTV and a 6 carbon ion fractions deliver 18Gy (RBE) to the GTV. For joint optimization, the total prescriptions are converted to BE; additional objectives are to limit the dose received by normal brain to an effect equivalent to a photon dose of 50Gy in 25 fractions, a 5mm CTV margin conformity objective, and minimization of the mean BE in normal brain. A photon alpha/beta of 10 and 2 is assumed for tumor and normal tissue, respectively.

Figure 1 shows the optimized combination of carbon ion fractions (b), photon fractions (d), and their cumulative effect converted to equi-effective dose in 2Gy photon fractions (f). For comparison, sub-figures (a), (c) and (e) show the treatment scheme used in the CLEOPATRA trial. Corresponding cumulative Effect Volume Histograms are shown in Figure 2. Overall, the optimal combination exhibits better conformity, for comparable target coverage and reveals that the dose delivered to the CTV (outside of the GTV) is almost entirely delivered by photons. Compared to the simple combination of the CLEOPATRA trial, the optimized combination increases the carbon ion dose contribution in the centre of the GTV by more than 100% and reduces the photon dose accordingly. At the boundary of GTV and CTV, the photon contribution is increased, resulting in a 16% reduction of mean effect to the normal tissue in the CTV.

Carbon ions and photons have distinct physical and biological advantages. Joint optimization of both modalities yields the optimal combination of carbon ions and photons that may best exploit each modality''s advantage and improve on a naive combination of the two modalities.