Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience

Abstract

Background The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma and the radionecrosis risk in this setting remain unclear. Objective To perform a large retrospective study to help inform proper indications, efficacy, and anticipated complications of SRS for recurrent glioblastoma. Methods We retrospectively analyzed patients who underwent Gamma Knife SRS between 1991 and 2013. We used the partitioning deletion/substitution/addition (partDSA) algorithm to identify potential predictor covariate cut points and Kaplan-Meier and proportional hazards modeling to identify factors associated with post-SRS and post-diagnosis survival. Results 174 glioblastoma patients (median age 54.1 years) underwent SRS a median of 8.7 months after initial diagnosis. Seventy-five percent had one treatment target (range = 1–6) and median target volume, and prescriptions were 7.0 cm3 (range 0.3–39.0) and 16.0 Gy (range 10–22), respectively. Median overall survival was 10.6 months following SRS and 19.1 months after diagnosis. Kaplan-Meier and multivariable modeling revealed that younger age at SRS, higher prescription dose, and longer interval between original surgery and SRS are significantly associated with improved post-SRS survival. Forty-six patients (26%) underwent salvage craniotomy after SRS, with 63% showing radionecrosis or mixed tumor/necrosis versus 35% showing purely recurrent tumor. The necrosis/mixed group had lower mean isodose prescription compared to the tumor group (16.2 vs 17.8 Gy, P = .0031) and larger mean treatment volume (10.0 vs 5.4 cm3, P = .0091). Conclusion Gamma Knife may benefit a subset of focally recurrent patients, particularly those who are younger with smaller recurrences. Higher prescriptions are associated with improved post-SRS survival and do not seem to have greater risk of symptomatic treatment effect.

Current status and recent advances in reirradiation of glioblastoma

“…With respect to the retrospective nature and small numbers of patients, available data suggest increased survival rates with SRS and systemic therapies compared to SRS alone [ 38 , 44 , 46 , 48 , 51 ]. The reported overall survival time after concurrent SRS and temozolomide is around 9–15 months; some [ 44 , 46 , 48 , 51 ], but not all [ 36 , 47 ], studies showed significant survival benefit following chemoradiation over SRS alone, especially in patients with O 6 -methylguanine-DNA methyltransferase (MGMT) gene promoter methylation. Since its approval by the US Food and Drug Administration for the treatment of patients with recurrent GBM in 2009, the efficacy of the anti-vascular endothelial growth factor (VEGF)-A humanized monoclonal antibody bevacizumab in combination with SRS has been evaluated in several studies [ 38 , 50 , 52 ].…”

Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas

“…Kong et al reported a RN rate of 24% and Imber et al of 16% after EBRT with 60 Gy in 2 Gy fractions and a single fraction re-irradiation with 16 Gy. This is equal to a summed EQD2 of 120 Gy and a BED of 200 Gy 3 for late reacting tissue [ 22 , 23 ]. Based on historical data, radiogenic complications after SBT alone occurred in 9% for tumors with a diameter < 4 cm and higher complication rates (up to 25%) were reported for tumors harboring larger diameters (≥ 4 cm) [ 9 ].…”

Research progress on radiotherapy technology and dose fraction scheme for advanced gliomas

“…However, this trial was discussed, because SRS was conducted before external radiation, and carmustine was not used as a routine treatment in GBM patients. Some subsequent retrospective studies on SRS revealed that SRS can be used as a safe and effective treatment for HGG patients with small recurrent tumors (44)(45)(46). Morris et al (47) reported that 45 patients with recurrent GBM were treated with SRS and bevacizumab.…”