1. Principal Author, MD Second Author, MD PhD Third Author, MSc Institution, City, Country 23 January 2013

2.  Glioblastoma Multiforme (GBM) is the most common primary brain malignant neoplasm in adults  Despite constant attempts to improve outcome, the survival of patients with GBM remains limited  Currently, the standard of care consists of maximal safe surgical resection followed by External Beam Radiotherapy (EBRT) and concomitant TMZ followed by adjuvant TMZ

3.  Post-operative EBRT:  60 Gy/30 daily fractions over 6 weeks  PTV margins extending to 2 to 2.5 cm from oedema/residual disease and surgical cavity  Dose response curve  Souhami, L. et al, 2004. RTOG 9305 for SRS boost in addition to conventional EBRT  Laperrière, N. et al, 1998. Interstitial Implant in addition to conventional EBRT

4.  IMRT  Concomitant boost technique Shorten overall treatment time: reduces accelerated repopulation Larger dose/fraction: increases cell killing  MRI co-registration  Immobilization  Treatment delivery verification  IGRT  Limited margins: reduce the normal brain volume irradiated  Reduction of treatment-related toxicity

5.  Temozolomide XRT+Temozolomide Temozolomide  Neo-adjuvant TMZ: 75 mg/m² QD will be administered for 2 weeks before starting radiotherapy  Accelerated Radiotherapy: 60 Gy in 20 fractions over 4 weeks using IMRT concomitant boost technique  Concurrent TMZ with accelerated hypofractionated radiotherapy: 75 mg/m² QD for the whole duration of radiotherapy  Adjuvant TMZ: 150 mg/m² QD for 5 consecutive days of a 28 day-cycle