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Glioblastoma Multiforme (GM) is the most frecuent primary malignant tumor in the central nervous system. It still has a poor prognosis. Only 30 % of the patients survive more than one year , and 5% of them, more than five years. Surgery is the first step in treatment, with complete resection if possible. Radiotherapy is the first adjuvant treatment option. Conventional treatment is 60 Gy total dose, 2 Gy per day. The association of adjuvnat RT and concurrent Temozolomide improves overall survival, in comparation with RT alone: 14.6 mounths vs 12.1 mounths. Surgical reintervention and reirradiation increase global survival from 6 to 10 months. Bevacizumab (BCB), alone or in association with Lomustine or Irinotecan, has an important anti-edema effect. It is indicated in recidivant Glioblastoma. To analized the tolerance and overall survival in patients with Glioblastoma Multiforme treated with hypofractionates and intensified radiotherapy, in a phase II prospective trial, is our purpose

Between january 2016 and may, 2020 we have treated 89 GM patients, 60 men (67%) a 29 women (33%) with Intensity Modulated Radiation Therapy (IMRT) . Median age was 60.1 (31-83 years old). 54 patients were treated wit total/subtotal surgical resection (60%). 35 patients werw only biopsied (45%) All of them received IMRT, in 20-25 fractions, (24.5 median fractions) in a dose escalated phase II trial, from a total dose of 66 Gy, to 76 Gy in biopsied patients. (EQD2 80 Gy), as follows: PTV1 : 50 Gy in 2 Gy per fraction. PTV2 , as a concurrent boost receiving 66-76 Gy (median 68 Gy) 2.2 – 3 Gy per fraction. 75 patients received concurrent Temozolomide 75 mg/m², 69 patients of them received at least three adjuvant Temozolomide cycles (Stupp protocol) Organs at risk were delimited: Braim stem, chiasm and optical nerves, motor cortex, pyramidal path, pituitary and cerebrum. After treatment, follow-up were done every 3 mounth with MRI . After clinical and/or radiological progression, patients with good performance status underwent: - Chemotherapy 28 patients (58%) : 12 patients CPT-11-BCB; 8 patients BCB alone; 2 patients Lomustine. - Re RT: 14 - Surgical reintervention: 7

Hypofractionated and intensified radiotherapy was well tolerated. 95 % of the patients finished the treatment All the breaks during radiation treatment were produced by the disease. During the follow-up, MRIs were performed every 3 months. Compatible changes due to treatment /radionecrosis, unable to rule out progression, were observed in 45% of patientes who underwent surgery, 74 % of biopsied patients, and the 85% of reirradiated patients. Overall Survival (OS) measured, starting on the first day of RT, in months: -Mediam global survival was 19 months (3-60 months) - In the group of patients who underwent surgery OS: 25 months (3-60 months) -In the group of biopsied patients OS was 12 months (2-28 months) -In the reirradiated group OS was 39 months. Seven patients underwent sugical reintervention. OS: 19 months (3-60 months) 5 of them glioblastoma were observed in pathological study, in the other two, necrosis and post radiation changes were informed. In this group OS is 54 months (p>0.2)

Hypofractionated and intensified radiotherapy improves OS in patients with Glioblastoma Multiforme, compared to conventional treatment (Stupp ). This treatment double the survival in the biopsied group and triples in reirradiated and reinterventioned groups