BACKGROUND: Prior retrospective and prospective studies suggest improved survival with the use of stereotactic radiosurgery (SRS) and bevacizumab in the treatment of limited-volume glioblastoma (GBM) recurrences. METHODS: We retrospectively reviewed our experience with gamma knife SRS in combination with bevacizumab for the treatment of focal GBM recurrence during 2009-2015. Outcomes include overall survival, progression free survival (PFS), and radiation-related adverse events. Kaplan-Meier methods and multivariable Cox proportional hazards models were performed for survival analysis. RESULTS: Within a median of 13.7 months after diagnosis, a total of 45 patients with GBM underwent gamma knife SRS and bevacizumab treatment. Median age was 57 years (range: 20-78 years) and 63.3% were women. The median Karnofsky Performance Score (KPS) at recurrence was 80 (range: 40-100). Sixty-four percent of patients had single radiosurgery target (range: 1-4) and median target volume and margin dose were 2.2 cm3 (range: 0.1-25.2 cm3) and 17.0 gray (Gy) (range: 13-24 Gy), respectively. Median PFS and overall survival were 9.3, 31.0 months following diagnosis, and 5.2, 13.3 months after SRS, respectively. Factors associated with poor outcomes were KPS ≤70, SRS dose <18 Gy, and use of <2 chemotherapy agents prior to SRS. No radiation-related adverse events occurred. CONCLUSIONS: SRS in combination with bevacizumab can be safely used to treat focal GBM recurrence. KPS, radiation dose, and multi-agent chemotherapy usage prior to SRS demonstrated significant impact on PFS. Bevacizumab may provide clinically relevant radioprotection.
Bevacizumab/therapeutic use , Brain Neoplasms/therapy , Glioblastoma/therapy , Neoplasm Recurrence, Local/therapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Radiosurgery/methods , Salvage Therapy/methods , Young Adult
Many cancers have similar aberrations in various signaling cascades with crucial roles in cellular proliferation, differentiation, and morphogenesis. Dysregulation of signal cascades that play integral roles during early cellular development is well known to be a central feature of many malignancies. One such signaling cascade is the Wnt/ß-catenin pathway, which has a profound effect on stem cell proliferation, migration, and differentiation. This pathway is dysregulated in numerous cell types, underscoring its global oncogenetic potential. This review highlights regulators and downstream effectors of this receptor cascade and addresses the increasingly apparent crosstalk of Wnt with other tumorigenic signaling pathways. As understanding of the genetic and epigenetic changes unique to these malignancies increases, identifying the regulatory mechanisms unique to the Wnt/ß-catenin pathway and similarly aberrant receptor pathways will be imperative.
