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OBJECTIVES: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. PATIENTS AND METHODS: Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥60, age ≥18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. RESULTS: All patients have completed the treatment protocol. Median age was 64,5 years (range 41-82 yrs) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. CONCLUSIONS: The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant TMZ, but the prognosis remain poor. In most cases the recurrence occurs within 7-9 months after primary treatment and up to 90% in close proximity to the resection cavity or the target volume of postoperative RT. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irrradiation or systemic agents, but no standard of care exists. MATERIALS AND METHODS: This is a retrospective analysis of 91 consecutive patients with GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy. The pattern of recurrence and salvage therapy (re-operation, re-irradiation, chemotherapy or supportive care), evaluated by interdisciplinary neuro-oncology team, was analyzed for all patients. The salvage radiotherapy was performed with hypo fractionated stereotactic technique with a total dose of 25 Gy in 5 consecutive fractions. RESULTS: At the time of data analysis, 74 out 91 patients had died and the tumour progression was the primary cause of death in 65 patients. Among 17 patients still alive, 11 were in stable disease and 6 in course of systemic salvage therapy. Recurrence occurred “in-field” in 59 patients (80%), and “out-field” in 14 patients (20%). At the time of recurrence, re-operation was performed in 6 patients, chemotherapy in 37 patients, best supportive care in 13 patients and salvage RT was in 15 patients. The median time interval between primary RT and salvage RT was 10.8 months (range, 6-54 months). The median overall survival was 17 months, 16.8 months, 9.9 months and 33 months for patients treated with re-surgery, chemotherapy, best supportive care and re-irradiation, respectively. In salvage RT patients, KPS (p = 0.03) and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status (p= 0.02) were statistically correlated with OS. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation dose without interruption. Neurological deterioration occurred in two patients at 1 and 3 months after re-irradiation and was managed successfully with dexamethasone. CONCLUSION: The current literature suggests that hypo-fractionated stereotactic radiation therapy is effective and safe in recurrent GBM after conventional chemo-radiation treatment. Until prospective randomized trials consolidate these results, the decisions for salvage treatment will remain individual and should be based on multidisciplinary analysis of each patient.