**Part 3**

**Therapeutic Advances** 

272 Advances in the Biology, Imaging and Therapies for Glioblastoma

Wehbe, K., Pineau, R., Eimer, S., Vital, A., Loiseau, H. & Deleris, G. (2010) Differentiation

Wei, J., Barr, J., Kong, L.-Y., Wang, Y., Wu, A., Sharma, A.K., Gumin, J., Henry, V., Colman,

Weizsaecker, M., Deen, D.F., Rosenblum, M.L., Hoshino, T., Gutin, P.H. & Barker, M. (1981)

Yiin, J.J., Schornack, P.A., Sengar, R.S., Liu, K.W., Feng, H., Lieberman, F.S., Chiou, S.H.,

Zhang, D., Feng, X.Y., Henning, T.D., Wen, L., Lu, W.Y., Pan, H., Wu, X. & Zou, L.G. (2009)

Zhou, J., Tryggestad, E., Wen, Z., Lai, B., Zhou, T., Grossman, R., Wang, S., Yan, K., Fu, D.X.,

targeted to CD105. *Eur. J. Radiol*., 70 (1): 180-9. ISSN:0720-048X

imaging. *Analyst,* 135(12): 3052-9. ISSN:0003-2654

*Neurol.,* 224(3): 183-192. ISSN:0340-5354

9 (4): 929-41. ISSN:1535-7163

ISSN:1078-0432

ISSN:1078-8956

between normal and tumor vasculature of animal and human glioma by FTIR

H., Sawaya, R., Lang, F.F. & Heimberger, A.B. (2010) Glioma-associated cancerinitiating cells induce immunosuppression. *Clin. Cancer Res.*, 16(2): 461-473.

The 9L Rat Brain Tumor: Description and Application of an Animal Model. *J.* 

Sarkaria, J.N., Wiener, E.C., Ma, H.I. & Cheng, S.Y. (2010) ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain. *Mol. Cancer Ther.*,

MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes

Ford, E., Tyler, B., Blakeley, J., Laterra, J. & van Zijl, P.C. (2011) Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogeneous proteins and peptides. *Nature Medicine*, 17(1): 130-4.

**14** 

*Turkey* 

**Stereotactic Radiosurgery for Gliomas** 

The idea of stereotactic radiosurgery (SRS) was first conceived in 1951 by Swedish neurosurgeon Lars Leksell. Focus of his idea was to destroy the surgically inaccessible intracranial tissues or lesions with single fraction high-dose radiation obtained from multiple radiation beams directed to target by stereotactic instruments. He designed the first prototype of gamma knife with Larsson in the light of this idea and performed on his first patient in a nuclear building in 1967. Device was installed at Sophiahemmet hospital in Karolinska – Sweden in the following year. Although only a limited number of patients were treated with gamma knife until 80's, the technique became more popular afterwards and pervaded all around the world. By the time, different radiosurgical devices were

SRS was also used in the management of gliomas as well as many other intracranial lesions for years. Some data acquired despite the lack of reported large case series and long term follow up results. Gliomas are believed to arise from neuroglial cells which encounter the most frequent intracranial tumors in different series, constitute 45-60% of all intracranial tumors. Gliomas have astrocytic, oligodendroglial, ependymal and mixed subtypes. They are also graded I to IV according to histological and clinical behavior. Whereas the grade I and II are accepted as "low grade", the grade III and IV are "high grade" gliomas (Louis et al., 2007). However a portion of low grade gliomas (LGG) are curable by means of current multimodal treatment techniques, the main goal in high grade gliomas (HGG) is the prolongation of survival with a high quality of life as much as possible. Besides, the malignant transformation of LGGs is a well-known issue. Extensive surgical resection followed by radiation therapy (RT) and chemotherapy is the golden standard within most of the treatment protocols; particularly for HGGs. Currently, there are many ongoing clinical studies focused on the role of SRS in the management of gliomas. In most cases, the

The term "radiotherapy" refers to the treatment of malignant neoplasms and some benign situations by ionizing radiation. The history of RT goes back almost to the exploration of radiation. Many techniques have been developed for performing RT over time which made the RT more accurate and lesion targeted. Recently, techniques such as 3D conformal RT provided by multileaf-collimators and intensity modulated RT are available in addition to conventional RT. External beam radiotherapy (EBRT) is frequently performed in multiple low-dose fractions for post-surgical residuals or recurrences in the management of gliomas.

developed (Pollock & Brown, 2005; Stieber & Ellis, 2005).

treatment protocols should be individualized.

**1.1 Radiotherapy versus radiosurgery** 

**1. Introduction** 

Mehmet Tönge and Gökhan Kurt *Gazi University, Department of Neurosurgery* 
