P09.36 A new therapeutic strategy for newly diagnosed glioblastoma patients: hypofractionated stereotactic radiation therapy (HSRT) delivered in 15 fractions respect to standard fractionation in 30 fractions, with concomitant temozolomide chemotherapy - A phase II study
Authors: P. Navarria, F. Pessina, S. Tomatis, M. Simonelli, A. Santoro, A. Ascolese, E. Clerici, M. Rossi, L. Bello, M. Scorsetti
Journal: Neuro-Oncology (2017)

Introduction: The standard of care, for newly diagnosed glioblastoma multiforme (GBM), consists of surgical resection, followed by radiotherapy with concurrent and adjuvant Temozolomide. Results are still unsatisfactory. Aim of this prospective study was to evaluate outcome of newly diagnosed GBM patients treated with hypofractionated stereotactic radiation-therapy (HSRT), with concurrent and adjuvant Temozolomide following maximal surgical resection. Materials and Methods: Patients 18-70 years old, Karnofsky performance scale (KPS) ≥70, and tumor up to 10 cm were included. Surgery was performed in all patients with the aim to maximally remove the tumor. Extent of resection (EOR) was defined as gross-total-resection (GTR) >99%, near-total-resection (NTR) 90-99%, and subtotal-resection (STR) ≤89%. For radiation therapy plan the dose prescriptions was 60 Gy/4 Gy fraction/15 fractions (BED10 84 Gy) on the surgical cavity and eventually residual tumor after surgery, and 42 Gy/2.8 Gy fraction/15 fractions (BED10 53.76 Gy) on the FLAIR MRI abnormality before surgery. All patients received concurrent and adjuvant TMZ. Clinical outcome was assessed by neurological examination, neuropsychological evaluation and MRI, at 1 months after CHT-HSRT and every 2 months thereafter. Response was recorded using the Response Assessment in Neuro-Oncology (RANO) working group. Results: Form September 2013 to November 2015, 105 patients with newly diagnosed GBM were enrolled in this phase II study which it was closed because the expected enrollment was achieved. Among them 100 were the evaluable patients and 5 were lost to follow up. Thirty-six (36%) were female and 64 (64%) male with a median age of 61 years (range 23-74 years). At admission, the most of patients had KPS 90-100 (75.5%) and were in RPA class V (83.67%). All tumors were IDH wild type; methylated MGMT was present in 61 (61%) GBM and unmethylated in 39 (39%). GTR was performed in 40 (40%) patients, NTR in 24 (24%), STR in 26 (26%), and biopsy in 10 (10%). Following surgery, all 100 patients received concurrent chemo-hypofractionated-radiotherapy and adjuvant TMZ for a median of 9 cycles. No severe peri-operative morbidity occurred and during RT neurological status remained stable. No Grade III-IV radionecrosis occurred. Neuropsychological evaluation before and after HSRT remained stable and QoL satisfactory. Hematologic toxicity was recorded in 12/100 (12%) patients. The median PFS time, the 1 and 2 years PFS rare were 20 months, 68.9% and 44.7%, respectively; the median OS time, the 1 and 2 years OS rate were 15.8 months, 71.6% and 29.7%. On univariate and multivariate analysis, age, KPS and the EOR were recorded as significantly conditioning survival (p<0.01). CONCLUSION: Surgical resection followed by hypofractionated radiation therapy with concurrent and adjuvant temozolomide is a safe and feasible treatment with promising perspectives.