New potential treatment protocol for radiotherapy of glioblastoma

Sammanfattning: Purpose: Improvements in mortality rate of glioblastoma patients have been limited during the past decades, due to the tumor’s rapidly growing and infiltrative behavior and resistance to current therapy. Recent findings show that higher brain mean dose strongly correlates with inferior overall survival and that local recurrences mainly occur centrally in previously irradiated regions. This project investigates the possibility of a new radiotherapy protocol for glioblastoma patients, where treatment margins are reduced in order to reduce brain dose while still cover the volume most prone to relapse. Method: Treatment plans from 45 patients who had been previously treated for glioblastoma, with a prescribed dose of 60 Gy/30 fractions, were used. Recurrence volumes (RV’s) were present for all patients. New treatment plans were produced, but with 1 cm clinical target volume (CTV) margins instead of 2 cm (current standard). Additional plans were created for 20 patients, for which a simultaneous integrated boost (SIB) of 75 Gy/30 fractions to the tumor volume was added to the reduced margins tratment plans. The boost volume was defined as a 2 mm margin to a union of the gross tumor volumes (GTVs) from MRI- and PET-scans. The 1 cm CTV was kept with the previous ordinated dose of 60 Gy. Comparison of doses to target volumes, RV’s and OAR’s were performed using the Wilcoxon signed rank test in combination with identity plots. Spearman’s rank correlation coefficient was used to find whether there is a correlation between the reduction in PTV volume and reduction of brain mean dose as well as dose coverage of RV’s and GTV. Results: Astatistically significant reduction in doses was found for whole brain (p<0.001), left eye (p=0.003), right hippocampus (p=0.03) and remaining OAR’s (p<0.001). No difference was found for RV’s (p=0.30) and PTV (p=0.22). Increased dose coverage was found for GTV (p=0.03) due to some outliers. A statistically significant correlation was found between reduction in brain mean dose and reduction in PTV volume (r=0.4, p=0.006). Evaluating treatment plans with SIB, no significant difference in doses were found for the eyes and hippocampi. The remaining OAR’s experienced statistically significant dose reductions (right optic nerve at p=0.005, the rest at p<0.001), while the target volumes and RV’s received increased dose coverages (p<0.001). Conclusion: Reducing the CTV margin from 2 cm to 1 cm may lead to better sparing of OAR’s without sacrificing dose coverage of target and RV’s. However, clinical trials would need to show whether this would change the recurrence patterns. These will be necessary to find whether the increased local dose coverage following a SIB would actually result in improved tumor control, since we have shown that OAR sparing was not sacrificed. Nonetheless, reducing the irradiated volume without increased treatment side effects would still be of benefit for the patient.