Abstract
BACKGROUND: Recurrence invariably occurs in patients with high-grade glioma (HGG) despite maximal definitive therapy. Currently, there is no standard-of-care salvage treatment approach and re-irradiation is considered an option for select patients. Various radiotherapy fractionation schedules have been investigated, including the use of stereotactic radiosurgery (SRS). The aim of this study was to provide clinical practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS) specific to salvage SRS for recurrent-HGG. We define SRS as focal radiation in a single fraction and hypofractionated radiosurgery (HFSRS) as focal radiation delivered over 2-5 fractions. METHODS: A literature review and meta-analysis were performed according to PRISMA guidelines. Recommendations were formulated according to DELPHI methodology. RESULTS: Sixty-two studies met the eligibility criteria for analyses, resulting in 2640 recurrent HGG patients. Stereotactic radiosurgery to a median total dose of 16 Gy was performed in 75% of patients, and HFSRS to the remaining 25% with a median total dose and number of fractions of 25 Gy and 5 fractions, respectively. The median overall survival from re-irradiation was 10.2 months. The pooled neurological toxicity rates were lower with HFSRS compared to SRS (4% vs. 7%, P = 0.001). A cumulative EQD2 greater than 120-130 Gy was significantly associated with a greater risk of radiation necrosis (P = 0.003). CONCLUSIONS: Focal re-irradiation with 16 Gy in single fraction or 24-25 Gy in 3-5 fractions, is safe and appears to be effective for recurrent-HGG. We also present clinical practice recommendations on behalf of the ISRS. Given the limited prospective data, no definitive conclusions can be drawn.