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In recurrent glioblastoma (GB) no standard therapeutic approach is reported, so surgery, chemotherapy and reirradiation could be proposed. Recently Regorafenib was approved for recurrent GB. The present retrospective study was conducted to evaluate safety and efficacy of re-irradiation with radiosurgery o stereotactic radiotherapy (SRS/SFRT) in patients with recurrent GB in association to Regorafenib.

Inclusion criteria were as follow: histological diagnosis of GB; carrying out primary/adjuvant chemo-radiotherapy treatment; magnetic resonance imaging (MRI) evidence of recurrent disease according to Response Assessment in Neuro-Oncology (RANO) criteria after primary/adjuvant treatment; good performance status. All patients underwent re-RT with SRS/SFRT with a median dose of 24 Gy (range 18-36 Gy) and median fractions of 5 (range 1-6), Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months.

From November 2019 to December 2021, 16 patients (6 women and 10 men) affected by GB recurrence were treated by re-RT plus Regorafenib. The median time occurred between primary/adjuvant RT and disease recurrence was 8 months (range 2-20). Moreover, in 6 cases (40%) a second surgery was performed and in other 6 cases a third RT was administered. At the time of the analysis, 11 patients were dead for disease. The median OS and PFS after recurrence were 8 and 6 months. Regarding SRS/SFRT toxicity no acute or late neurological side effect grade ≥ 2 were reported. No case of radio-necrosis was detected. One patient that received Regorafenib after 45 days from re-surgery, suffered by surgical wound dehiscence, requiring the chemotherapy interruption. Grade 3-4 hematologic toxicity occurred in 5 cases, asthenia occurred in all patients.

Re-RT with SRT/SFRT in association with Regorafenib is a safe and feasible treatment and a combined ones as a better option for selected patients.