Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience

Abstract

BackgroundThe current standard of care for salvage treatment of glioblastoma multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival.MethodsFrom 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18–35 Gy (median 25) in three to five fractions via CyberKnife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof.ResultsThe median overall survival (OS) from date of recurrence was 8 months (2.5–61) and 5.3 months (0.6–58) from the end of fSRT. The OS at 6 and 12 months was 47 and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49, and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV <36 cc, recursive partitioning analysis <5, and Eastern Cooperative Oncology Group performance status <2 were all associated with improved survival (P < 0.05). There was no evidence of radionecrosis for any patient.ConclusionRadiation Therapy Oncology Group (RTOG) 1205 will establish the role of re-irradiation for recurrent GBM, however our study suggests that CyberKnife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status, or long interval from diagnosis.

Sense and sensibility to early combine bevacizumab to radiation treatment of brain metastasis: reply to Lou and Sperduto

“…However, many BM patients are eligible to SRS and it could be assumed that the good safety profile of BEV administration with a large radiation volume may also be expected in the context of its combination with smaller volume as in SRS. This assumption seems confirmed by some recent data of SRS combined with BEV in patients with recurrent malignant gliomas, confirming the feasibility of this approach with a good safety profile (5)(6)(7)(8). Clinical evaluation of BEV combined with SRS through a prospective trial is urgently needed for patients with BM.…”

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

“…At the time of recurrence, TMZ has been proven to be an effective salvage therapy, with bevacizumab emerging as a potential replacement [3, 9]. MGMT methylation appears to play a role, as prolonged TMZ therapy can substantially deplete MGMT.…”

“…Surgical treatment of a focal recurrence can lead to prolonged growth control and reduced tumor burden and is favored in younger patients with an initial prolonged disease-free interval in whom recurrence is solid or cystic, circumscribed, and has not infiltrated other vital structures [1, 4, 6, 7]. While previous studies have suggested that surgical resection provides a palliative and local control benefit, prolonged survival has not been observed [8, 9]. Chemotherapy agents have been used with limited success as trials of bevacizumab and irinotecan have demonstrated efficacy in delaying tumor recurrence with minimal long-term benefit, especially after recurrence [6, 10, 11].…”

Stereotactic Radiotherapy in Recurrent Glioblastoma: A Valid Salvage Treatment Option

“…Reoperation was performed in 7 cases before they were referred to our clinic; in 6 cases, it was subtotal resection and in 1 case it was gross total resection. SRT was performed in a median of 3 fractions (range 2-5) and the median prescription dose was 20 Gy (range [18][19][20][21][22][23][24][25][26][27][28][29][30], which was biologically equivalent to a dose of 40 Gy (range 28.8-52.8). The SRT parameters were as follows: the median conformity index, the new conformity index, and the homogeneity index were calculated as 1.23 (range 1.08-2.52), 1.29 (range 1.12-7.54), and 1.19 (range 1.09-1.43), respectively.…”

“…in a median of 3 fractions (range 2-5). The median prescription dose was 20 Gy (range [18][19][20][21][22][23][24][25][26][27][28][29][30]. While the median actuarial survival after initial diagnosis for patients treated with salvage SRT was 30 months (range 9-123), it was only 14 months (range 1-111) for patients who could not be treated with salvage SRT (p = 0.001).…”