Surgical Resection Of Glioblastoma Research Articles

P08.64 5-ALA fluorescence-guided surgical resection of glioblastoma in the elderly

P08.64 5-ALA fluorescence-guided surgical resection of glioblastoma in the elderly

Factors associated with increased survival after surgical resection of glioblastoma in octogenarians.

Elderly patients with glioblastoma represent a clinical challenge for neurosurgeons and oncologists. The data available on outcomes of patients greater than 80 undergoing resection is limited. In this study, factors linked to increased survival in patients over the age of 80 were analyzed. A retrospective chart review of all patients over the age of 80 with a new diagnosis of glioblastoma and who underwent surgical resection with intent for maximal resection were examined. Patients who had only stereotactic biopsies were excluded. Immunohistochemical expression of oncogenic drivers (p53, EGFR, IDH-1) and a marker of cell proliferation (Ki-67 index) performed upon routine neuropathological examination were recorded. Stepwise logistic regression and Kaplan Meier survival curves were plotted to determine correlations to overall survival. Fifty-eight patients fit inclusion criteria with a mean age of 83 (range 80–93 years). The overall median survival was 4.2 months. There was a statistically significant correlation between Karnofsky Performance Status (KPS) and overall survival (P < 0.05). There was a significantly longer survival among patients undergoing either radiation alone or radiation and chemotherapy compared to those who underwent no postoperative adjuvant therapy (p < 0.05). There was also an association between overall survival and lack of p53 expression (p < 0.001) and lack of EGFR expression (p <0.05). In this very elderly population, overall survival advantage was conferred to those with higher preoperative KPS, postoperative adjuvant therapy, and lack of protein expression of EGFR and p53. These findings may be useful in clinical decision analysis for management of patients with glioblastoma who are octogenarians, and also validate the critical role of EGFR and p53 expression in oncogenesis, particularly with advancing age.

RT-35 * ELAPSED DAYS AFTER RADIOTHERAPY FOR GLIOBLASTOMA

BACKGROUND: There have been conflicting reports regarding the effect of delayed radiation therapy after surgical resection of glioblastoma (GBM) on outcomes. We sought to investigate whether the timing of adjuvant radiotherapy (RT) impacted survival of patients at our institution. METHODS: We reviewed all patients treated with radiotherapy for GBM at our institution. Variables included in our analysis were age, Karnofsky Performance Status (KPS), type of surgery, length of hospital stay, receipt of temozolomide (TMZ), RT duration, RT technique, total RT dose, interval between surgery and RT, and tumor molecular status including isocitrate dehydrogenase 1 (IDH-1) and O-6-methylguanine-DNA methyltransferase (MGMT). Survival was calculated using the Kaplan-Meier Method. RESULTS: From 1998 to 2013, 419 GBM patients were treated with radiotherapy of which 239 were men (57.0%). The median age was 60 years (range 18–91). The median survival for the entire cohort was 339 days (11.1 months). 151 patients started radiotherapy after surgery 5 weeks (20.8%). On univariate analysis age, KPS, type of surgery, length of hospital stay, RT duration, RT technique, total dose and interval between surgery and RT were significant predictors of mortality. IDH-1 (p = 0.17) and MGMT (p = 0.18) mutated status showed a trend towards better survival. Patients who started RT 5 weeks after surgery with the 1-year actuarial overall survival: 52.4%, 63.6% and 63.9%, respectively. On multivariate analysis only age, KPS, type of surgery, and total RT dose were significant predictors of survival; while interval between surgery and RT was not. CONCLUSIONS: We observed no detriment to delaying RT after surgical resection of GBM, and in fact, a small benefit to deferring RT until 3 weeks after surgery was observed on univariate analysis.

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma

The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].