title: Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.
abstract: OBJECTIVE
  To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT).
  
  
  METHODS
  We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months.
  
  
  RESULTS
  The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas.
  
  
  CONCLUSIONS
  The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Antonio José
authors.initials: AJ
authors.lastname: Conde-Moreno
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: García-Gómez
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Albert-Antequera
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Piedad
authors.initials: P
authors.lastname: Almendros-Blanco
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: De Las Peñas-Bataller
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: González-Vidal
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: López-Torrecilla
authors.affiliation: Consorcio Hospitalario Provincial de Castellón, Avda. Doctor Clarà 19, 12002 Castellón, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrer-Albiach
keywords: ASCO, American Society of Clinical Oncology; BVZ, bevacizumab; Bevacizumab; CAT, computed axial tomography; CI, confidence interval; CPT11, irinotecan; CR, complete response; CTCAE, common terminology criteria for adverse events; FLAIR, fluid-attenuated inversion recovery; FSRT, fractionated stereotactic radiotherapy; Fractionated stereotactic radiotherapy; GTV, gross tumour volume; HGG, high-grade glioma; HR, hazard ratio; High-grade glioma; KPS, Karnofsky Performance Scale; MGMT, O-6-methylguanine-DNA methyltransferase; MRI, magnetic resonance imaging; NA, not applicable; OS, overall survival; PD, progressive disease; PET, positron emission tomography; PFS, progression-free survival; PR, partial response; PTV, planning target volume; RANO, revised Assessment in Neuro-Oncology; Rescue treatment; SD, stable disease; SEOM, Sociedad Española de Oncología Médica; SRS, stereotactic radiosurgery; TMZ, temozolomide; VEGF, vascular endothelial growth factor