The integrin antagonist cilengitide has been explored as an adjunct with 
anti-angiogenic properties to standard of care temozolomide chemoradiotherapy 
(TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as 
anecdotal clinical observations indicate that anti-angiogenic treatment may 
result in altered patterns of tumor progression. Using a standardized approach, 
we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 
2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. 
Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal 
TMZ trial served as a reference. MRIcro software was used to map location and 
extent of initial preoperative and recurrent tumors on MRI of both groups into 
the same stereotaxic space which were then analyzed using an automated tool of 
image analysis. Clinical and outcome data of the cilengitide-treated patients 
were similar to those of the EORTC/NCIC trial except for a higher proportion of 
patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene 
promoter. Analysis of recurrence pattern revealed neither a difference in the 
size of the recurrent tumor nor in the distance of the recurrences from the 
preoperative tumor location between groups. Overall frequencies of distant 
recurrences were 20 % in the reference group and 19 % (4/21 patients) in the 
cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide 
does not alter patterns of progression. This analysis does not support concerns 
that integrin antagonism by cilengitide may induce a more aggressive phenotype 
at progression, but also provides no evidence for an anti-invasive activity of 
cilengitide in patients with newly diagnosed glioblastoma.