SURGICAL THERAPIES
M. Aghi, M. A. Vogelbaum, D. J. Jolly, J. M. Robbins, D. Ostertag, C. E. Ibanez, H. E. Gruber, N. Kasahara, K. Bankiewicz, T. F. Cloughesy, S. M. Chang, N. Butowski
(+205 others)
2013
Neuro-Oncology
We are conducting investigational dose escalation trials in patients with High Grade Glioma (HGG, NCT01156584 and NCT01470794), using a retroviral replicating vector (Toca 511). Toca 511 (vocimagene amiretrorepvec) encodes an optimized yeast cytosine deaminase that converts 5-fluorocytosine (5-FC) to the anti-cancer drug 5-FU in infected tumors. We report here results of a Phase 1/2 trial of direct intratumoral Toca 511 administration to recurrent HGG patients, followed by repeat courses of
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... 5-FC. Six Toca 511 dose levels, escalated by half logs, the mode of administration and the use of extended release 5-FC (Toca FC) were investigated in 25 HGG patients to date. Treatment at all dose levels has been well tolerated. Post-treatment resection in two patients showed viral protein and DNA and RNA sequences including the CD gene, suggesting viral spread and persistence. MRI and clinical improvements were also occasionally observed. Virus was initially delivered via a brain biopsy needle and placement in the tumor was predicted using conventional neuro-navigation. Immediate MRI after injection of Toca 511 spiked with gadolinium showed inconsistent delivery of Toca 511 to tumors. As a result, real-time MRI-guided delivery was introduced using Toca 511 infusion with a stepped-tip cannula. Using this approach, delivery into as many as 4 locations of up to 3 mL of Toca 511 at flow rates of up to 30 mL/min has been achieved without reflux. In a tumor biopsy from a patient who received 1 mL of Toca 511 and subsequent Toca FC, we observed tumor selective vector transduction and expression by PCR and RT-PCR with concomitant tumor necrosis. At higher Toca 511 doses, significant MRI changes consistent with tumor regression were observed post-Toca FC dosing. Completion of this study is planned, including dose escalation of Toca 511 and increasing the dose and duration of Toca FC. ST-002. ENDOSCOPIC PITUITARY TUMOR SURGERY: THE LEARNING CURVE BACKGROUND: Data from SIOP CNS GCT 96 and other trials suggest improved outcome with delayed resection of residual tumour in patients with intracranial NGGCTs. The relevance of tumor site on this management algorithm has not been evaluated. METHODS: Until 31.05.2012, 200 patients with NGGCT were treated according to SIOP CNS GCT 96. Median Abstract iii218 NEURO To evaluate the results of stereotactic biopsy for deep seated intraaxial lesions. PATIENTS AND METHODS: Sixteen patients with intraaxial lesions suspected of brain tumor. The locations of lesions were, deep white matter of cerebrum 4, basal ganglia 1, thalamus 6, midbrain 2, pons 3. Patients age range was 9 -81 years (median 61 years), and 9 were men and 7 were women. Under local anesthesia the Leksell stereotactic frame was fixed and the MRI were taken. To determine the targets, neuroimages such as enhanced CT scan or PET study were also used as references. After image acquisition patients were transferred to OR and under general anesthesia, several samples were taken with 2.1mm diameter needle by aspiration. Most Abstract NEURO-ONCOLOGY † N O V E M B E R 2 0 1 3 iii219 at Olson Library, Northern Michigan University on October 15, 2014 http://neuro-oncology.oxfordjournals.org/ Downloaded from Abstract iii220 NEURO-ONCOLOGY † N O V E M B E R 2 0 1 3 at Olson Library, Northern Michigan University on October 15, 2014 http://neuro-oncology.oxfordjournals.org/ Downloaded from Abstract iii222 NEURO-ONCOLOGY † N O V E M B E R 2 0 1 3 INTRODUCTION: IDH gene mutation was frequently found in anaplastic gliomas. Although IDH gene mutation has been reported to be a favorable prognostic factor, anaplastic gliomas with IDH gene mutations sometimes recurred as secondary glioblastoma. In this study, we investigated the role of BACKGROUND: The standard of care for patients with newly diagnosed gliblastoma multiforme (GBM) is surgical resection followed by radiation and temozolomide chemotherapy. Treatment regimens at the time of tumor recurrence, which occurs in virtually all patients, have not been standardized and repeat surgical resection (re-operation) is considered in only one in four patients. METHODS: This retrospective study comprised 97 consecutive patients who were deemed favorable candidates for re-operation on the basis of previously validated prognostic criteria. Multivariate analyses were carried out to identify pre-and post-operative clinical and radiographic variables independently associated with overall survival after re-operation. Volumetric area under the curve (AUC) analysis of 619 serial post-operative magnetic resonance imaging (MRI) studies (median 4 per patient) was performed to determine the regrowth rate of tumors following re-operation. RESULTS: The median post-operative survival of all patients following re-operation was 12.4 months (95% CI,). In a multivariate analysis, progressively larger post-operative residual tumor volume was Abstract iii224 NEURO-ONCOLOGY † N O V E M B E R 2 0 1 3 at Olson Library, Northern Michigan University on October 15, 2014 http://neuro-oncology.oxfordjournals.org/ Downloaded from independently associated with decreased survival (p , 0.001), along with greater age (p ¼ 0.003) and lower pre-operative Karnofsky performance status (KPS) (p , 0.001). Larger volume residual tumors had higher rates of subsequent regrowth (p ¼ 0.003), and a higher regrowth rate in turn independently associated with decreased survival (p , 0.001). CONCLUSIONS: The median survival of patients re-operated for recurrent GBM compares favorably to historical controls. Re-operation should be considered in all patients who meet favorable pre-operative clinical and radiographic criteria. For patients undergoing re-operation, the surgical goal should be to leave a minimal amount of residual tumor tissue in order to slow tumor regrowth and maximize survival benefit. Abstract NEURO-ONCOLOGY † N O V E M B E R 2 0 1 3 iii225 at Olson Library, Northern Michigan University on October 15, 2014 http://neuro-oncology.oxfordjournals.org/ Downloaded from
doi:10.1093/neuonc/not191
fatcat:ktiejra7nzhk7lowmcblsgyggy
