title: Glioblastoma: patterns of recurrence and efficacy of salvage treatments.
abstract: BACKGROUND
  It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.
  
  
  METHODS
  We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.
  
  
  RESULTS
  58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).
  
  
  CONCLUSIONS
  The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.
authors.affiliation: Divison of Neurology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Oh
authors.forename: Arjun
authors.initials: A
authors.lastname: Sahgal
authors.forename: Paul
authors.initials: P
authors.lastname: Sanghera
authors.forename: May N
authors.initials: MN
authors.lastname: Tsao
authors.forename: Phil
authors.initials: P
authors.lastname: Davey
authors.forename: Kelvin
authors.initials: K
authors.lastname: Lam
authors.forename: Sean
authors.initials: S
authors.lastname: Symons
authors.forename: Richard
authors.initials: R
authors.lastname: Aviv
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000379:methods; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D000077204:Temozolomide; D014057:Tomography, X-Ray Computed
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide