Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas

Abstract

Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity.

Methods and materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed.

Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival.

Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach.

Fig. 1

Overall survival (A) and progression-free survival (B) from the time of salvage sterotactic radiosurgery (SRS) for patients with a recurrent World Health Organization Grade 4 glioma who did (+) or did not (−) receive adjuvant bevacizumab (BVZ).

Fig. 2

Overall survival from the time of stereotactic radiosurgery (SRS) for patients with a World Health Organization Grade 3 or 4 glioma who had a Karnofsky performance status (KPS) >70 compared with patients with a KPS ≤70.

Fig. 3

Overall survival (A) and progression-free survival (B) from stereotactic radiosurgery (SRS) in patients with World Health Organization Grade 4 glioma who had experienced progression while receiving bevacizumab before radiosurgery and who did or did not receive additional bevacizumab at the time of or shortly after salvage radiosurgery.