PurposeGlioblastoma Multiforme (GBM) is the most common malignant brain tumor and frequently recurs in the same location after radiotherapy. Intensive treatment targeting localized lesion is required to improve GBM outcome, but dose escalation using conventional methods is limited by healthy tissue tolerance. Helical Tomotherapy (HT) Dose Painting (DP) treatments were simulated to safely deliver high doses in the recurrent regions. Materials and methodsApparent Diffusion Coefficient (ADC) data from five recurrent GBM were retrospectively considered for planning. Hypo-fractionated (25−50Gy, 5 fractions) voxel-based prescriptions were opportunely converted to personalized structured-based dose maps to create DP plans with a commercial Treatment Planning System. Optimized plans were generated and analyzed in terms of plan conformity to dose prescription (Q0.90–1.10), tolerance of the healthy tissues (DMAX), and dosimetry accuracy of the deliverable plans (γ-index). ResultsOnly three of the five cases could receive a safe retreatment without violating the maximum critical organs dose constraints. The conformity of the simulated plans was between 40.9% and 79.9% (Q0.90–1.10), their delivery time was in the range of 38.3–63.6min, while the dosimetry showed γ-index of 82.4–92.4%. ConclusionsThis study proved the ability of our method to simulate personalized, deliverable and dosimetrically accurate DPBN plans. HT hypo-fractionated treatments guided by ADC maps can be realized and applied to deliver high doses in the GBM recurrent regions, although there are some critical issues related to low Q0.90–1.10 values, to exceeding of healthy-tissue dose constraints for some patients and long delivery times.