Salvage radiosurgery for high grade glioma in the era of modern systemic therapy.

surgical resection followed by radiotherapy combined with concurrent and adjuvant temozolomide for glioblastomas and radiotherapy for grade 3 gliomas, local relapse remains the predominant pattern of failure for high grade gliomas. Several studies have reported greater than 70% of recurrences occurring within 2 cm of the original gadolinium-enhanced mass after concurrent radiation and temozolomide.1,2 Given the high incidence of local recurrence within the region of prior highdose radiotherapy, there have been a number of studies investigating the role of radiosurgery for recurrent high grade glioma. These include studies of radiosurgery using gamma knife, linac and cyberknife technology.3-7 This paper reports a retrospective single institution experience of 33 patients treated with Gamma Knife radiosurgery for focally recurrent, high grade gliomas.8 Studies evaluating the role of radiosurgery for focally recurrent glioblastoma have demonstrated longer survival than studies evaluating other salvage treatments but this is likely due to patient selection bias. A recent pooled analysis of 300 patients accrued to the European Organization for Research and Treatment of Cancer (EORTC) Brain Tumor Group phase I or II trials for recurrent glioblastoma explored prognostic factors associated with overall and progression-free survival. The following prognostic factors were associated with overall survival (OS) and progressive-free survival (PFS): World Health Organization (WHO) performance status (p < 0.0001), presence of neurological deficits (p = 0.0002), baseline administration of steroids (p < 0.0001), number of target lesions (p < 0.0001), tumour size (largest tumour diameter, p < 0.0001), and frontal tumour location (p = 0.02).9 Considering these factors, patients who are eligible for radiosurgery at the time of their glioblastoma multiforme (GBM) recurrence generally have good performance status, single or few small tumours that do not require corticosteroids to manage symptoms. These are all recognized prognostic factors in patients with recurrent GBM. There have also been reports of prognostic factors specifically associated with improved outcomes after salvage radiation. These include younger age, higher Karnofsky performance status (KPS) and better recursive partitioning analysis (RPA) class and lack of steroid dependence, smaller and unifocal tumour targets, use of higher radiation prescription dose, the extent of pre-radiosurgery tumour resection, and use of concurrent chemotherapy. Increased time to tumour recurrence has also been associated with better outcomes.10-16 Considering all these factors, the patients included in this study had particular favorable prognostic factors with a high average KPS of 85.2 prior to radiosurgery, small average tumour volume of only 4.4 cm3 (range: 1.1 15.7 cm3) and long duration between initial