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BACKGROUND/AIM Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG. PATIENTS AND METHODS We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9). RESULTS Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p

Bevacizumab has demonstrated activity in patients with recurrent glioblastoma. However, the impact of prognostic factors associated with recurrent glioblastoma treated with cytotoxic agents has not been determined in patients treated with bevacizumab. To analyze the prognostic factors and clinical benefits of bevacizumab and irinotecan treatment in patients with recurrent glioblastoma. This monocentric study retrospectively analyzed all patients with recurrent glioblastoma who were treated with at least one cycle of bevacizumab and irinotecan at our institution from April 2007 to May 2010. Multivariate analysis was used to analyze prognostic factors for overall survival (OS) from the initiation of bevacizumab administration. Among the 100 patients that were identified (M/F: 65/35), the median age was 57.9 years (range: 18–76). Karnofsky Performance Status (KPS) was

Purpose The management of glioblastoma multiforme (GBM) in elderly patients with poor performance status is not well established. A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken. Patients and Methods Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score (KPS) less than 70 were eligible for this nonrandomized phase II trial. Treatment consisted of 150 to 200 mg/m2/d temozolomide for 5 days every 4 weeks until disease progression. Radiotherapy was not administered. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, quality of life, and cognition. Results Seventy patients (median age, 77 years; median KPS, 60) were enrolled between July 2007 and February 2009. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13% and 14% of patients, respectively. Median PFS was 16 weeks (95% CI, 10 to 20 weeks), and median OS was 25 weeks (95% CI, 19 to 28 weeks), comparing favorably with a 12- to 16-week OS expected from a purely supportive approach. Twenty-three patients (33%) improved their KPS by 10 or more points, and 18 (26%) became capable of self-care (KPS ≥ 70). Overall quality of life and cognition improved over time before disease progression. In the 31 tumors evaluated for O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation, a methylated status indicated longer PFS (26 v 11 weeks; P = .03) and OS (31 v 19 weeks; P = .03). Conclusion Temozolomide has an acceptable tolerance in elderly patients with GBM and KPS less than 70. It is associated with improvement of functional status in 33% of patients and appears to increase survival compared with supportive care alone, especially in patients with methylated MGMT promoter.

BACKGROUND: Predictive marker of bevacizumab activity is an unmet medical need. We evaluated predictive value of selected circulating prebiomarkers involved in neoangiogenesis and invasion on patient outcome in recurrent high grade glioma (HGG) treated with bevacizumab. METHODS: A set of eleven prebiomakers of interest (VEGF, VEGF-R2, bFGF, SDF1, PlGF, uPA, PAI1, MMP2, MMP7, MMP9, and adrenomedulline) were analyzed in plasma, using ELISA, at baseline and 2 weeks apart from bevacizumab initiation in a prospective cohort of 26 patients (Cohort1). Correlations were validated in a separate retrospective cohort (Cohort2;n = 50) and tested in cohort patients treated with cytotoxic agents without bevacizumab (Cohort3;n = 34). Dosages were correlated to objective response (OR), Progression-free survival (PFS), and overall survival (OS). In cohort 1, multiple time points were performed up to progression. Additionally MMP2 and MMP9 plasma levels were analyzed in patients with newly diagnosed GB, after surgery. Finally, MMP2 and 9 RNA were assessed in tumor tissue of a separated group of paired newly diagnosed and recurrent GB (n = 29). RESULTS: In cohort1, high MMP2 baseline level was associated to a probability of OR of 83.3% versus 15.4% in case of low MMP2 level (p = 0.001). In multivariate analysis, baseline level of MMP2 correlated with PFS (hazard-ratio(HR), 3.92; 95% confidence-interval(CI):1.46-10.52; p = 0.007) and OS (HR, 4.62; 95%CI 1.58-13.53; p = 0.005), as decrease of VEGF (p = 0.038 for PFS and p = 0.013 for OS) and MMP9 (p = 0.016 for PFS and p= 0.025 for OS). In cohort2, MMP2, but not MMP9, confirmed its predictive significance. In cohort3, no association was found between MMP2, MMP9 and outcome. In cohort 1, significant changes in MMP2 and MMP9 plasma levels were observed during treatment. MMP2 increased after Bev initiation (p = 0.002), and decreased at progression (p = 0.002) while MMP9 initially decreased (p = 0.007) then increased at progression (p = 0.031). No significant difference was observed both for plasma level and tissue RNA expression between newly diagnosed and recurrent GB. CONCLUSIONS: In patients with recurrent HGG treated with bevacizumab, but not with cytotoxic agent, high MMP2 plasma levels are associated with prolonged tumor control and survival, while changes over time may reflect tumor control. Comparison of MMP2/MMP9 levels between initial diagnosis and recurrence may suggest that bevacizumab could be similarly effective in this two setting. MMP2 should be tested in randomized clinical trials that evaluate bevacizumab efficacy, and its biological role reassessed. SECONDARY CATEGORY: Clinical Neuro-Oncology.

BACKGROUND: In grade II and codeleted grade III gliomas, the procarbazine-CCNU-vincristine (PCV) combination increase survival when added to radiotherapy as first line treatment, despite the important toxicity of this treatment schedule. Our objective was to analyze the tolerance, feasibility and impact of dose intensity of the PCV regimen on outcome for patients with OG. METHODS: We retrospectively reviewed all grade III OG patients receiving PCV (CCNU:110mg/m2) who were referred to our two institutions. The total dose and dose adaptation, cycle delay, dose intensity, toxicity and premature discontinuation of CCNU were analyzed. Impact of these factors on patient outcome was evaluated. RESULTS: Between 2007 and 2011, 89 patients received PCV. Only 37% completed 6 cycles, whereas 13.4% prematurely discontinued PCV because of toxicity. Cycle delay and dose reduction were observed for 62% and 70% patients, respectively. Grade 3 and 4 toxicities were observed in 38% and 8% patients, respectively. Among patients who did not progress under PCV regimen, by multivariate analysis, premature discontinuation for toxicity was significantly correlated with poor PFS (p = 0.023, Hazard ratio (HR):2.354) and OS (p = 0.021, HR:5.093). By univariate analyses, absence of CCNU dose adaptation was correlated to poor PFS (p = 0.032). For OS, pejorative factors were high total CCNU dose (p = 0.029), absence of cycle delay (p = 0.009), absence of CCNU dose adaptation (p = 0.020) and grade 3/4 toxicities (p = 0.013). High CCNU dose-intensity tended to poorly impact PFS (p = 0.053) and OS (p = 0.112). By multivariate analysis, absence of CCNU dose adaptation remained significant for PFS (p = 0.001), while OS was negatively impacted by the absence of cycle delay (p = 0.049) and grade 3/4 toxicities (p = 0.045). CONCLUSION: Despite the efficacy of the PCV regimen, significant toxicity is associated with this schedule, which appears to impact its feasibility and efficacy. The optimal PCV schedule should be redefined taking into account this finding.

A 7-year-old Lebanese girl with recently diagnosed relapsing polychondritis had a 1-month history of several painful ulcerations involving her entire body. Skin biopsy was consistent with the diagnosis of pyoderma gangrenosum. She was hospitalized and started on intravenous steroids with partial improvement. During her hospital stay, she developed right wrist drop. Radiologic studies revealed a large aortic aneurysm and an axillary aneurysm compressing the right brachial nerve plexus. Pathology of the resected aortic anyeurism confirmed the diagnosis of Takayasu's arteritis. The patient was started on infliximab therapy with complete resolution of her skin lesions and improvement in hand function.

e13017 Background: Secondary leptomeningeal gliomatosis (LMG) is a rare and severe progression pattern of glioma. Prognostic factors and therapeutic management of this pattern remains unclear. Our objective was to evaluate characteristics and outcome of LMG patients (pts). Methods: We retrospectively reviewed pts diagnosed with secondary LMG referred to our institution between 2004 and 2013. Diagnosis was obtained by clinical, imaging and cerebrospinal fluid (CSF) data. Results: The identification and diagnosis of 31 pts with LMG was based on CSF cytology (n=12), on MRI data (n=16) with hyperproteinarrachia (>1.2 gr/l) (n=9) or without (n=7), or on meningism with hyperproteinarrachia (n=3). At LMG diagnosis (LMGD), median age was 45 years and Karnofsky Performance Status (KPS) was

2024 Background: Predictive marker of Bev activity is an unmet medical need. We evaluated predictive value of selected circulating prebiomarkers involved in neoangiogenesis and invasion on patient outcome in recurrent HGG treated with Bev. Methods: A set of eleven prebiomakers of interest (VEGF, VEGF-R2, bFGF, SDF1, PlGF, uPA, PAI1, MMP2, MMP7, MMP9, and adrenomedulline) were analyzed in plasma, using ELISA, at baseline from Bev initiation in a prospective cohort of 26 patients (Cohort1). Correlations were validated in a separate retrospective Bev treated cohort (Cohort2; n = 50) and then tested in a cohort of patients treated with cytotoxic agents without Bev (Cohort3; n = 34). Dosages were correlated to OR, PFS, and OS. MMP2 and MMP9 were then analyzed at multiple time points up to progression. Results: In cohort1, high MMP2 baseline level was associated with an OR rate of 83.3% for high levels versus 15.4% for low MMP2 levels (p = 0.001). In multivariate analysis, MMP2 baseline level was correlated with PFS (hazard-ratio (HR), 3.92; 95% confidence-interval (CI):1.46-10.52; p = 0.007) and OS (HR, 4.62; 95%CI 1.58-13.53; p = 0.005), as MMP9 (p = 0.016 for PFS and p = 0.025 for OS). Similar results were found in cohort2 for MMP2, (MMP2: p

Background Predictive marker of bevacizumab activity is an unmet medical need, while activity of this anti-VEGF Mab is reported to be heterogeneous, particularly in glioblastoma. Objective To identify circulating biomarker that predicts response to bevacizumab and outcome in recurrent high grade glioma (HGG). Methods Eleven angiogenic makers were analyzed, using ELISA, at baseline and one month apart from bevacizumab initiation in a first cohort of 26 HGG patients of our institution (cohort 1); Plasma marker dosages were correlated to objective response (RANO criterias), Progression-free survival (PFS), and overall survival (OS). Correlations were validated in a separate cohort of 50 patients (Cohort 2). Markers analyses were performed in two other cohorts treated with cytotoxic agents up front (cohort 3 n = 20) or concomitant to radiotherapy (cohort 4 n = 24). Results In cohort 1, high MMP2 baseline level was associated to a probability of response of 83.3% versus 15.4% in case of low MMP2 level (p = 0.001). By univariate analyses, confirmed by multivariate analysis, MMP2 correlated with PFS (p = 0.007) and OS (p = 0.001), as decrease of plasmatic VEGF level (p = 0.038 for PFS and p = 0.013 for OS) and MMP9 level (PFS p = 0.016, OS p = 0.025). These results were confirmed with a similar magnitude in cohort 2 for MMP2 only (p Conclusions Among patients with recurrent HGG treated with bevacizumab, but apparently not with cytotoxic agent, higher plasma MMP2 levels were associated with objective response, prolonged tumor control and survival. Further studies are needed to validate the predictive value of these/this biomarker(s) both with glioma and other cancers. Disclosure O. Chinot: Roche consultant. All other authors have declared no conflicts of interest.

2060 Background: Chemosensitivity of OAG has been documented although their role as part of adjuvant treatment combined to radiotherapy is debated. Beside temozolomide still under investigation, several studies have underlined activity of PCV regimen in this setting. However, significant toxicity has been described and dose intensity and schedule duration are not clearly reported. Methods: This monocentric retrospective analysis included all pts with OAG treated with at least 1 cycle of PVC (lomustine 110mg/m2 every 6 weeks) at our institution from August 2007 to August 2011 (pharmacy charter). Toxicities data were collected from clinical observations and blood investigations. Results: 40 pts were identified (M/F: 23/17). Median age was 45y (20 – 72). At the time of analyses, 32 pts were still alive. Histologies were oligodendroglioma (73%) or oligoastrocytoma (27%). Codeletion 1p19q was observed in 30 % of pts. PCV was administered in first or second line of chemotherapy for 60 % and 40 % of pts respectively. Seventy five percent and 52.5% of pts completed at least of 4 and 6 cycles respectively. Discontinuation of PCV occurred in 45% of pts for toxicity (10%), progression (30%), or other reason (5%). Because of toxicity 38/196 (19%) PCV cycles were delayed. Dose was adapted for 73% of pts and decreased under 60% of theoretical dose in 30% of pts at cycle 4 and in 57% of pts at cycle 6 (table1). Grade III or IV toxicity occurred in 28% of pts and only grade I-II in 50%. Neuropathies occurred in 43 % of pts. Conclusions: Despite activity of PCV regimen, significant toxicity is associated to this schedule, that impact feasibility and compliance. PVC schedule should be redefined taking into account dose intensity applied in toxicity observed. [Table: see text]

2091 Background: Bevacizumab (BEV) with or without irinotecan (IRI) have demonstrated activity in patients with recurrent GBM. However, conflicting results raise the implication of BEV in facilitating infiltrative progression associated with a shorter survival. While Pope et al. (Neuro-Oncol, 2009) proposed 4 pattern of disease progression, it appear that these pattern definition may not fully identify the “gliomatosis phenotype progression”. We tested a more extensive anatomical analysis as previously described in gliomatosis cerebri (Peretti, J Neuro-Oncol, 2002) Methods: Consecutive MRI performed every 2 months from 25 patients with recurrent GBM treated with BEV+IRI were retrospectively analysed. Status (Local, multifocal, diffuse), number of lobes involved, and tumor infiltration of corpus callosum (CC), basal ganglia or thalamus (BG) and brainstem (BS) were analysed at the time of BEV-+IRI initiation up to progression. Results: At the time of BEV+IRI initiation, 9 (36%), 11 (44%), and 5 (20%) pts pr...

2087 Background: Bevacizumab (BEV) with or without irinotecan (IRI) have demonstrated activity in patients with recurrent GBM. However, survival benefit is debated. In order to explore clinical benefit and impact of BEV administration on survival, we analysed clinical outcome of patients treated with BEV +IRI in our institution, according to initial RPA classes, and recognized prognostic factors at recurrence. Methods: This single center retrospective cohort analysis included all patients with recurrent GBM treated with at least 1 cycle of BEV+IRI at our institution from April 2007 to May 2010, based on pharmacy charter. Overall survival was analysed from initial diagnosed of GBM (OS1) and from initiation of BEV+IRI (OS2). Progression free survival (PFS2) was analysed from initiation of BEV+IRI. Patients were assigned to RPA classes at the time of initial diagnosis as defined by Mirimanoff and col. (JCO, 2006) Results: 100 pts were identified, (M/F: 65/35), with a median age of 57.9 y (18-76). At the time...