Results of a multicenter survey showing interindividual variability among neurosurgeons when deciding on the radicality of surgical resection in glioblastoma highlight the need for more objective guidelines.

PURPOSE: We assessed agreement among neurosurgeons on surgical approaches to individual glioblastoma patients and between their approach and those recommended by the topographical staging system described by Shinoda. METHODS: Five neurosurgeons were provided with pre-surgical MRIs of 76 patients. They selected the surgical approach [biopsy, partial resection, or gross total resection (GTR)] that they would recommend for each patient. They were blinded to each other's response and they were told that patients were younger than 50 years old and without symptoms. Three neuroradiologists classified each case according to the Shinoda staging system. RESULTS: Biopsy was recommended in 35.5-82.9%, partial resection in 6.6-32.9%, and GTR in 3.9-31.6% of cases. Agreement among their responses was fair (global kappa = 0.28). Nineteen patients were classified as stage I, 14 as stage II, and 43 as stage III. Agreement between the neurosurgeons and the recommendations of the staging system was poor for stage I (kappa = 0.14) and stage II (kappa = 0.02) and fair for stage III patients (kappa = 0.29). An individual analysis revealed that in contrast to the Shinoda system, neurosurgeons took into account T2/FLAIR sequences and gave greater weight to the involvement of eloquent areas. CONCLUSIONS: The surgical approach to glioblastoma is highly variable. A staging system could be used to examine the impact of extent of resection, monitor post-operative complications, and stratify patients in clinical trials. Our findings suggest that the Shinoda staging system could be improved by including T2/FLAIR sequences and a more adequate weighting of eloquent areas.

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma.

PURPOSE: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. PATIENTS AND METHODS: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. RESULTS: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. CONCLUSIONS: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.

Clinical course of high-grade glioma patients with a "biopsy-only" surgical approach: a need for individualised treatment.

INTRODUCTION: 'Biopsy-only' high-grade glioma (HGG) patients get limited benefit from post-operative treatments, and as a group, negatively impact median survival outcomes. MATERIAL AND METHODS: We retrospectively evaluated clinical characteristics, treatment and overall survival of HGG patients with a 'biopsy- only' surgical approach diagnosed between 1997 and 2005 at a University Hospital in Spain. RESULTS: In 31% of 294 suspected gliomas, only a diagnostic biopsy was undertaken. Reasons for 'biopsy-only' for all patients were either location in eloquent areas: (motor area 18.7%, language area 25,3%, basal ganglia 7.7%, visual area 4.4%) or extension of the disease (corpus callosum invasion 14.3% and multicentricity/multifocality 28.6%). Seventy-four patients (80.4%) were HGG: 26% of all grade IV and 49% of all grade III tumours. For these patients, post-operative Karnofsky Performance Status of over 70%, median age and median survival were, respectively: 64 and 70%, 60.7 and 57 years old, and 23.1 and 42.7 weeks (p=0.0006). Patients lived longer if post-operative treatment was given, in all grades (p<0.0001). Nineteen patients (25.6%) died within 42 days after surgery. Only 60% of them initiated radiotherapy and 10% of them did not complete it. However, tumour grade, radiotherapy and temozolomide- based chemotherapy were independently associated with longer survival in multivariate analysis (p<0.05). CONCLUSION: Almost one third of HGG patients can undergo only a biopsy and not debulking surgery. Although radiotherapy improves survival, only 50% of them complete the treatment. An individualised approach to these patients is needed to facilitate a correct analysis of therapy results. New therapies must be investigated in these patients.