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  • Radiation Sensitization of Glioma by Locally Delivered Cilengitide in a Rat Brainstem Glioma Model

    Final Number:

    Sina Tok; Betty Tyler BA; Jeanine Reyes; Momen Sharab; I-Mei Siu PhD; Vanessa Charubhumi; Robert Thomas Wicks BS, BA; Ulrich-Wilhelm Thomale MD; George I. Jallo MD, FACS

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Clinical trials are assessing efficacy and safety of systemic Cilengitide (CGT) for the treatment of high grade glioma in patients. We have previously shown that CGT delivered locally via osmotic pumps is safe and effectively prolongs survival in a rodent brainstem glioma model. We hypothesize that adding radiotherapy (XRT) to local CGT delivery will be safe and provide an added survival benefit over either therapy alone.

    Methods: F344 rats were injected with F98 glioma into the brainstem and were randomized to the following groups on day 5: 1) No therapy (n=8); 2) Local CGT (n=6); 3) XRT (n=8); 4) Low-dose local CGT and XRT (n=7); 5) Local CGT and XRT (n=7). The local delivery system consisted of an osmotic pump containing either CGT (1.6mg) or low-dose CGT (0.8mg) connected to a brain infusion kit and cannula placed in the brainstem at the site of tumor injection. XRT was applied once on day 5 with an external beam single-dose radiation treatment of 20 Gy.

    Results: Controls had a median survival of 13 days. The combined XRT and local CGT group showed significantly increased survival (p<0.01) with a median survival of 24 Days as compared to the control group. It showed no significant survival benefit (p=0.31) over XRT alone (median survival = 18.5 Days).

    Conclusions: These results suggest that a combination therapy of intracranial delivery of CGT via convection-enhanced delivery and XRT effectively prolongs survival in a rodent brainstem glioma model but does not seem to provide any survival benefit over XRT alone.

    Patient Care: This is preclinical research looking at the local delivery of cilengitide for the treatment of glioma.

    Learning Objectives: The reader should learn that locally delivered cilengitide in addition to radiation therapy may be a treatment option for those with glioma, however in this model did not appear more beneficial that XRT alone.


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