Upfront gamma knife with concomitant bevacizumab - a gamechanger in glioblastoma management?

Background Glioblastoma (GBM) carries an extremely poor prognosis and despite aggressive multimodality treatment the current median overall survival is only around 14 months. We wanted to evaluate the feasibility and early clinical outcomes and tumour control of Gamma Knife radiosurgery (GKRS) given concurrently with Bevacizumab in these patients, delivered either upfront (before surgery) or after surgery. Methods All Patients with histologically proven GBM (IDH wild Type) over a 36-month period (January 2023–December 2025) who were given GKRS with concomitant Bevacizumab (200 mg slow intravenously given within 2 h of the GKRS session) were enrolled prospectively in this study. Ethics permission was taken from the IRB (Approval number IEC-512/01/09/2023). As waiting time from diagnosis to surgery at our institution routinely exceeds 3 months for such patients, GKRS was offered upfront (based on radiological suspicion) and given to patients who consented. They were then operated when they got admitted as per the waiting list. Patients who declined upfront GKRS received GKRS after surgery. Patients who received EBRT, non-IDH wildtype tumors and patients with less than 6 months follow up were excluded from the study. Clinico-radiogical data was analyzed at baseline and on each follow-up. Results Eight patients were enrolled in the study period, of whom only three received the primary intervention, upfront GKRS before surgery; the remaining five received GKRS after surgery. The mean age was 45 years (20–74 years) with a male to female ratio being 3:1. The mean tumour volume during GKRS was 30 cc (range 2.1–71.3 cc). The median follow up was 12 months (range 6.7–37 months), with one, and two year overall survival being 100% and 80%. Conclusion This prospective pilot cohort represents one of the first reports describing upfront Gamma Knife radiosurgery with concomitant low-dose bevacizumab as a temporizing treatment strategy for patients with radiologically suspected IDH-wildtype glioblastoma awaiting delayed surgical intervention. The approach was technically feasible and well tolerated, with encouraging radiological and clinical observations in selected patients, particularly those experiencing prolonged delays before surgery . However, given the small sample size (only three patients received upfront GKRS), heterogeneous treatment sequencing, absence of randomization, and lack of a contemporaneous control group, these findings should be regarded as preliminary and hypothesis-generating. Larger prospective controlled studies are required to evaluate the safety, feasibility, and potential role of this strategy in carefully selected patients.