title: Distance to the neurooncological center: a negative prognostic factor in patients with glioblastoma multiforme. An epidemiological study.
abstract: BACKGROUND
  Regardless of current multimodal treatment strategies, the prognosis of patients harboring glioblastoma multiforme (GBM) is still dismal. The introduction of concomitant radiochemotherapy and adjuvant cyclic temozolomide has significantly improved the overall survival, compared to postoperative radiotherapy-alone. Furthermore this regimen shows a lower toxicity profile compared to previous nitrosourea-based chemotherapy and can easily be applied on an outpatient basis, thus potentially facilitating chemotherapy in rural and more remote areas. The distance to the oncological center has been shown to be a negative prognostic parameter in other types of cancer. Therefore, we aimed to investigate whether the introduction of temozolomide as the standard regimen in the treatment of GBM has influenced the administration of chemotherapy and the prognosis of patients depending on the distance to our neurooncological center.
  
  
  METHODS
  A total of 208 patients diagnosed with GBM (M:F=1.4:1), surgically resected between 1990 and 2009, thus covering the pre-temozolomide and the temozolomide-era, were included retrospectively in this analysis. The distance from the patients' residences to the neurooncological center was determined and statistical analysis was performed to assess its influence on overall survival and administration of adjuvant treatment (radiotherapy-only, nitrosourea-based chemotherapy and adjuvant temozolomide).
  
  
  RESULTS
  Overall, 41.3% of the cohort underwent subtotal surgical resection, whereas a gross total resection was accomplished in 57.2%. The median distance to the neurooncological center was 75 km (range=1-870 km). Postoperatively, 68 patients (32.7%) received concomitant and adjuvant radiochemotherapy with temozolomide, 31 (14.9%) were treated with nitrosourea other than the Procarbazin, Lomustin, Vincristin (PCV), 34 (16.3%) with PCV, and 71 patients (34.1%) had radiotherapy-alone. The distance to the neurooncological center had a significant influence on overall survival for the whole cohort (p=0.027) and patients with increasing distances, were significantly less often treated with chemotherapy (p=0.05). With the introduction of temozolomide this relation was lost (overall survival, temozolomide and other agents: p=0.685/p=0.007; administration of adjuvant chemotherapy in the temozolomide-era/whole cohort: p=0.612/p=0.05).
  
  
  CONCLUSIONS
  The distance to the neurooncological center negatively-influenced the prognosis of patients with GBM. Patients were less often treated with adjuvant chemotherapy in the pre-temozolomide era with increasing distance to the neurooncological center. Although the introduction of temozolomide as the standard chemotherapeutic agent in GBM treatment changed this fact, the influence of the distance to the specialized center should be kept in mind as a prognostic factor for this disease.
authors.affiliation: Department of Neurosurgery, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kerschbaumer
authors.forename: Christian Franz
authors.initials: CF
authors.lastname: Freyschlag
authors.forename: Richard
authors.initials: R
authors.lastname: Bauer
authors.forename: Alois Albert
authors.initials: AA
authors.lastname: Obwegeser
authors.forename: Gerrit Alexander
authors.initials: GA
authors.lastname: Schubert
authors.forename: Claudius
authors.initials: C
authors.lastname: Thomé
authors.forename: Marcel
authors.initials: M
authors.lastname: Seiz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D006297:Health Services Accessibility; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide