Background Assess benefit of salvage bevacizumab (BEV) at time of symptomatic progression in patients with refractory glioblastoma (GBM). Methods Patients managed with adjuvant long course chemo-radiation therapy for GBM were entered into a prospective database. At chemorefractory symptomatic progression, patients were offered BEV or best supportive care. Re-irradiation (ReRT) was used with BEV in selected patients. BEV continued indefinitely until deterioration limited hospital based infusion. The primary endpoint was median survival calculated from date of decision for BEV to proceed (BEVstart), or decision to decline BEV (BEVreject). Results Fifty-five patients were managed of which 48 patients have relapsed disease. The median survival post relapse was 6 months (95%CI: 4.6–7.4). At relapse, 28 patients received BEV with only 14% delivered at first relapse. The median number of BEV cycles was 8 (range 1–25). ReRT was subsequently used in 16 (33%) relapsed patients. BEV treated patients were associated with improved median survival post relapse with 9 months vs 3 months ( p < 0.01). The median survival from BEV related decision-making at symptomatic refractory progression to death was 4 months (95%CI: 2.0–6.0). BEVstart was associated with improved survival from this date with median survival of 6 months vs 1 month with BEVreject (p < 0.01). Median survival with ReRT from this date was 8 months vs 3 months without ReRT ( p = 0.01). In the BEV patients at eventual progression, death occurred at a median of 30 days post BEV cessation. Conclusion In this clinic managing selected patients with chemorefractory progressive glioblastoma, delayed salvage bevacizumab, often in combination with re-irradiation, may provide an increase in survival duration compared with best supportive care.

Objective There is minimal evidence to support decision-making for symptomatic steroid-refractory pseudoprogression or true progression occurring after IMRT for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or Bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM. Methods Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database. Patients with symptomatic steroid-refractory mass effect within 6 months of IMRT managed with either RedoSx or BEV were identified for analysis. For the primary endpoint of median overall survival (OS) post intervention, outcome was analysed in regards to potential prognostic factors, and differences between groups assessed by log-rank analyses. Results Of 399 patients managed with the EORTC-NCIC Protocol, 78 required an intervention within 6 months of IMRT completion for either true or pseudoprogression (49 with RedoSx and 29 with BEV). Subsequently 20 of the 43 patients managed with RedoSx when BEV was clinically available, required salvage with BEV within 6 months after RedoSx. Median OS post intervention was 8.7 months (95%CI: 7.84-11.61) for the total group; and 8.7 months (95%CI: 6.8-13.1) for RedoSx and 9.4 months (95%CI: 7.8-13.6) for BEV (p=0.38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (p=0.10).Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki67% reduction correlated with survival. Presence of pure necrosis and residual tumour cells only had improved survival compared with presence of gross tumour (p&lt;0.001). Conclusions At time of symptomatic steroid-refractory true or pseudoprogression following IMRT for GBM, BEV was equivalent to RedoSx in terms of OS. Pseudoprogression with residual cells at RedoSx was not associated with worse outcome compared to pure necrosis.

Delivery of highly sophisticated, and subspecialised, management protocols for glioblastoma in low volume rural and regional areas creates potential issues for equivalent quality of care. This study aims to demonstrate the impact on clinical quality indicators through the development of a novel model of care delivering an outsourced subspecialised neuro-oncology service in a regional centre compared with the large volume metropolitan centre. Three hundred and fifty-two patients with glioblastoma were managed under the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) Protocol, and survival outcome was assessed in relation to potential prognostic factors and the geographical site of treatment, before and after opening of a regional cancer centre. The median overall survival was 17 months (95% CI: 15.5–18.5), with more favourable outcome with age less than 50 years (p < 0.001), near-total resection (p < 0.001), Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1 (p < 0.001), and presence of O-6 methylguanine DNA methyltransferase (MGMT) methylation (p = 0.001). There was no difference in survival outcome for patients managed at the regional centre, compared with metropolitan centre (p = 0.35). Similarly, no difference was seen with clinical quality process indicators of clinical trial involvement, rates of repeat craniotomy, use of bevacizumab and re-irradiation. This model of neuro-oncology subspecialisation allowed equivalent outcomes to be achieved within a regional cancer centre compared to large volume metropolitan centre.