P08.44 Phase II study of hypofractionated radiation therapy with concomitant and adjuvant temozolomide following surgical resection for patients with newly diagnosed glioblastoma: preliminary evaluation

Abstract

INTRODUCTION: The current standard treatment for glioblastoma multiforme (GBM) has led a median, overall survival (OS) of 14.6 months, a 2-year progression-free survival (PFS) of 11% and a 2-year OS of 27.2%. The predominantly local failure pattern indicates the need to intensify local treatment. Radiation therapy dose escalation did not result in an improvement of tumor local control and patient survival. Hypofractionation could be an attractive alternative approach of dose intensification compared to dose escalation with conventional fractionation. It uses a higher dose per fraction to increase the biological effective dose, while shortening the overall treatment time. The aim of this phase II study is to evaluate safety and feasibility of hypofractionated RT in addition to chemotherapy, concomitant and adjuvant, following surgical resection, in patients with newly diagnosed GBM. METHODS AND MATERIALS: From September 2013 to February 2016, 120 patients with newly diagnosed GBM were enrolled. This is a preliminary evaluation of the first 49 patients treated. Inclusion criteria were patients aged 18-70 years with KPS ≤60, patients aged <70 years with KPS ≤80, histopathologically confirmed of GBM or WHO grade III glioma IDH1 wild type and no codeletion 1p19q, estimated survival ≤ 3 months, tumor or surgical cavity ≥ 10 cm in its greatest diameter (including FLAIR area). All patients underwent surgical resection followed by hypofractionated radiation therapy, concomitant and adjuvant chemotherapy with temozolomide. The total dose prescribed was 60 Gy/ 4 Gy fraction/15 fractions (BED10 84 Gy) on surgical cavity and eventual postoperative residual tumor on contrast-enhancing MRI and Methionine PET and 42 Gy/2.8 Gy fraction/15 fractions (BED10 53.76 Gy) on the preoperative abnormality on FLAIR MRI. Clinical outcome was evaluated by neurological examination and MRI 1 months after RT and then every 3 months. Response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: All 49 patients evaluated have carried out the treatment as planned and no interruption or severe toxicity occured. At the last observation time 15 (30.6%) patients are alive and 34 (69.4%) dead. The median, 1-and 2-year PFS were 14.9 months, 63% and 13.7%; the median, 1 and 2 years Disease-specific survival (DSS) were 16.2 months, 76.5% and 22.9%. Patients with age > 60 years, KPS 90-100, complete surgical resection, MGMT methylated status had better outcome with a median, 1 and 2 years DSS of 22.5 months, 85.7%, 33%; 22.4 months, 92%, 30%; 20.3 months, 86.9%, 35%; 20.3 months, 76.2%, 38.4% respectively. CONCLUSIONS: Hypofractionated radiation therapy is a safe and feasible treatment for patients with newly diagnosed glioblastoma.