title: Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  From 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Radiation 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.
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA.
authors.forename: Shaakir
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA.
authors.forename: Eda
authors.initials: E
authors.lastname: Chen
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Lanciano
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Nursing, University of Pennsylvania , Philadelphia, PA , USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Hanlon
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: John
authors.initials: J
authors.lastname: Lamond
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Arrigo
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: William
authors.initials: W
authors.lastname: Ding
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mikhail
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Ghaneie
authors.affiliation: Philadelphia CyberKnife/Crozer Keystone Healthcare System , Philadelphia, PA , USA ; School of Medicine, Drexel University , Philadelphia, PA , USA.
authors.forename: Luther
authors.initials: L
authors.lastname: Brady
keywords: glioblastoma multiforme; glioblastoma radiosurgery; glioblastoma stereotactic; recurrent glioblastoma; salvage stereotactic