The impact of anatomical changes during photon or proton based radiation treatment on tumor dose in glioblastoma dose escalation trials

Purpose/Objective: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. Material and Methods: For 24 glioblastoma patients a photon- and proton-based dose escalation treat ment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribu tion on this specific high dose region. Results: The median time between the planning MRI and additional MRI was 26 days (range 16–37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3–11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treat ment plans, respectively. Conclusion: Our study showed that only for a limited number of patients anatomical changes during pho ton or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvol ume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.