Re-irradiation for recurrent glioblastoma multiforme: a critical comparison of different concepts

PURPOSE: Purpose of this study was to investigate outcome and toxicity of re-irradiation for recurrent primary glioblastoma (rGBM). We evaluated a group of patients with rGBM and identical primary treatment comprising adjuvant radiotherapy (30 × 2 Gy) with concurrent temozolomide (TMZ).

METHODS: In this retrospective study of 46 patients, all received adjuvant or definitive normofractionated radiotherapy to a pretreated area, some with concurrent chemotherapy. Impact of different clinical, histological, or epidemiological factors on survival and radiation toxicity was reviewed.

RESULTS: Of 46 patients, 40 completed the intended therapy. Overall survival (OS) was 20 months (range 6-72 months). Overall survival and progression-free survival after re-irradiation (OS2 and PFS2) were 9.5 and 3.4 months (range 2-40 and 0.7-44 months). Simultaneous systemic therapy improved PFS2 and OS2 (4.3 vs. 2.0, p < 0.001 and 12 vs. 4 months, p = 0.13, respectively). Therapy with TMZ or bevacizumab improved PFS2 vs. nitrosureas (6.6 vs. 2.9, p = 0.03 and 5.1 vs. 2.9 months, p = 0.035, respectively). TMZ also improved PFS2 and OS2 vs. all other systemic therapies (6.6 vs. 4, p < 0.001 and 17 vs. 10 months, p = 0.1). In a subgroup analysis for patients with methylation of the MGMT promoter, doses of >36 Gy as well as TMZ vs. no systemic therapy improved PFS2 (p = 0.045 and p = 0.03, respectively). 27.5% of all patients had no acute toxicity. Three patients with acute and four patients with late grade 3 toxicities were reported.

CONCLUSION: Normofractionated radiotherapy is a feasible option for rGBM with a good toxicity profile. Simultaneously applied systemic therapy was associated with improved outcome. For MGMT promoter-methylated histology, higher radiation doses improved survival.