ABSTRACT
PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Brain Neoplasms/drug therapy , Carmustine/therapeutic use , Glioblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , AC133 Antigen/genetics , AC133 Antigen/metabolism , Adult , Aged , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Bevacizumab/adverse effects , Brain Neoplasms/blood supply , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Carmustine/adverse effects , Chitinase-3-Like Protein 1/genetics , Colombia , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Drug Administration Schedule , Female , Genes, erbB-1 , Genes, p53 , Glioblastoma/blood supply , Glioblastoma/genetics , Glioblastoma/mortality , Humans , Isocitrate Dehydrogenase/genetics , Male , Methylation , Middle Aged , Mutation , Neoplasm Recurrence, Local/blood supply , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Progression-Free Survival , RNA, Messenger/metabolism , Receptors, Platelet-Derived Growth Factor/genetics , Survival Analysis , Tumor Suppressor Proteins/metabolism , Young AdultABSTRACT
Long term research results initiated by Dr. P. I. Branemark in 1965 and before, had widely demonstrated that with an adequate biomaterial, a phenomenon of biological acceptance from maxillary bone occurs, configurating a real bone healing, obtaining an intimate bonding between this alive tissue and the implant, which will last under function. Nevertheless, for this bio-physiological step happens and remain, there are many necessary factors named biological and biomechanical principles, and they command and are the responsibles of the osseointegration success.
