Purpose: Despite the multidisciplinary approach, within 2 cm of the primary site, 77% of Glioblastoma Multiforme (GBM) will recur. Thus, higher radiation dose seems reasonable to improve local control. We reported the preliminary results of the treatment with concomitant hypofractionated Simultaneous Integrated Boost Intensity-Modulated Radiotherapy (SIB-IMRT) plus Temozolomide (TMZ) followed by adjuvant TMZ therapy in patients with newly diagnosed GBM to determine the safety, tolerability, and efficacy. Patients and Methods: Between January 2018 and February 2020, a total of 27 patients over the age of 18 years with newly diagnosed, histologically confirmed GBM were assigned to receive oral TMZ (75 mg/m2/d x 7 d/wk for 6 weeks, from the first to the last day of RT) with fractionated RT (2.4 Gy, 2.2 Gy, and 2.0 Gy per fraction to PGTV, PCTV high risk, and PCTV low risk, 5 d/wk, for a total of 64.8 Gy, 59.4 Gy and 54 Gy, respectively) followed by TMZ monotherapy (150 mg/m²/d to 200 mg/m²/d x 5 days, every 28 days for six cycles) at Clinical Oncology Department, Faculty of Medicine, Tanta University Hospital. The primary end point was overall survival; secondary end points were progression-free survival, safety and tolerability. The date of this analysis is February 2021. Results: At a median follow-up period of 20 months (range; 5-30 months), the median Progression-Free Survival (PFS) for all patients with GBM was 14 months, and the 2-year PFS rate was 19.2%. The median Overall Survival (OS) was 20 months and the 2-year OS rate was 40.8%. The mean age was 50.2 years (standard deviation ± 9.7284), and 44.4% of patients had undergone biopsy only. There was no mortality caused by drug toxicity. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. Conclusion: The addition of TMZ to hypofractionated SIB-IMRT followed by adjuvant TMZ was well tolerated and has shown promising activity in the treatment of newly diagnosed GBM. Further investigation is warranted. [ABSTRACT FROM AUTHOR]