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vi14 NEURO-ONCOLOGY • NOVEMBER 2016 combination with TMZ in recurrent refractory malignant brain tumors. METHODS: After progression on TMZ, patients are eligible for enrollment in this study of indoximod (1200 mg twice daily orally) combined with a standard fixed dose of TMZ (150mg/m2 x 5 days). In the phase 2 expansion, patients are enrolled into 3 cohorts: 2a: indoximod with TMZ (for patients refractory to TMZ), 2b: indoximod with TMZ and bevacizumab (for patients who have progressed on bevacizumab), 2c: indoximod with TMZ in conjunction with stereotactic radiosurgery in select patients. Indoximod is administered for all 28 days of each treatment cycle. ACTR-54. PHASE I TRIAL OF GENETICALLY MODIFIED HEMATOPOETIC PROGENITOR CELLS FACILITATING BONE MARROW CHEMOPROTECTION AND ENABLING TMZ/O6BG DOSE ESCALATION RESULTING IN IMPROVED SURVIVAL Andrew  Sloan1,2, Hua  Fung3, Jane  Reese-Kroc4, Lisa  Rogers5, Christopher Murphy6, Hilard Lazrus4, Boro Dropulic7 and Stanton Gerson4; 1Department of Neurological Surgery University Hospitals-Case Medical Center, Cleveland, OH, USA, 2Case Comprehensive Cancer Center, Cleveland, OH, USA, 3Case Western Reserve University School of Medicine, Cleveland, OH, USA, 4Case Western Reserve University SOM & Case Comprehensive Cancer Center, Cleveland, OH, USA, 5Case Western Reserve School of Medicine & Case Comprehensive Cancer Center, Cleveland, USA, 6University Hospitals-Seidman Cancer Center & Case Comprehensive Cancer Center, Cleveland, OH, USA, 7Lentigen Inc., Baltimore, MD, USA INTRODUCTION: Glioblastoma (GBM) is the most common malignant brain tumor with a median survival of 15 months despite surgery and aggressive radio-chemotherapy. The most important mechanism of TMZ resistance is the O6-methylguanine-DNA methyltransferase (MGMT) gene which repairs temozolamide-induced DNA methylation. The MGMT inhibitor O6-benzylguanine (BG) has demonstrated efficacy in depleting MGMT and maximizing tumor response in early phase clinical trials. However, because MGMT expression is also low in hematopoietic cells, this has resulted in unacceptable bone marrow toxicity, and this approach has been abandoned. We hypothesized that chemoprotection of hematopoieticprogenitor cells (HPC) with an MGMT mutant (MGMT-P140K) characterized by normal methyltransferase activity coupled with low affinity for BG, would maximize anti-tumor response while enabling patients to tolerate TMZ & BG dose escalation with minimal toxicity. We thus performed a phase I trial to test this hypothesis. METHODS: We treated 7 consecutive patients with newly diagnosed GBM with standard surgery and radiation, followed by transplantation with autologous CD34+hematopoetic progenitor cells engineered to express MGMT-P140K using a lentiviral vector in three arms. To assess chemo-protection, patients’ blood counts and transgene marking were monitored during the treatment as was tumor growth and survival. RESULTS: The viral transduction rates were 2.5–75% and were clearly improved in the third arm with intra-patient dose escalation. P140K-MGMT gene markings in peripheral blood and bone marrow cells increased 3-26fold with only mild-moderate (Grade 2–3) mylosuppression consistent with chemo-selection and chemo-protection as hypothesized. Survival ranged from 20–36 months which exceeded their RPA predicted survival by 1.9– 3.2 fold suggesting clinical benefit (mean 2.0). Viral insertion site analysis failed to demonstrate evidence of clonal dominance. CONCLUSION: These preliminary result demonstrates that this chemoprotection strategy is tolerable, safe, and facilitates TMZ & BG dose escalation resulting in increased survival in a small cohort of selected patients. A phase II study is planned. ACTR-55. ADVANCES IN MANAGEMENT OF LOW-GRADE GLIOMAS Sumul  Raval1,2, Victoria  Momyer1, Kelsey  Murray1 and Ruchi  Raval1; 1Garden State Neurology & Neuro-Oncology PC, West Long Branch, NJ, USA, 2David S. Zocchi Brain Tumor Center at MMC, West Long Branch, NJ, USA BACKGROUND: Low-grade gliomas (LGGs) are common brain tumors that arise from various glial cells of the brain. The complex and variable backgrounds of LGGs cause difficulties in assigning therapies. In this report, we compile findings relating to LGG genetics and treatment options in order to create a coherent summary for referential use. METHODS: We compiled 70 articles from the past ten years that cover a broad range of topics pertaining to LGGs, including molecular, genetic, epigenetic, morphological, and other diagnostic factors, as well as prognosis and treatment options. RESULTS: Molecular basis and histology of the tumor must be addressed for proper treatment. The 1p/19q co-deletion indicator has been considered the gold standard of glioma diagnosis and prognosis, but oft-sighted mutations in the IDH1 and IDH2 genes have given rise to three subgroups of 1p/19q co-deleted tumors, each associated with specific patterns of glial cells. Other molecular markers and microRNA expression patterns have been studied for possible diagnostic/prognostic methods. Microsurgical resection is the singular treatment with highest overall survival (OS) and quality of life (QOL). Total gross resection is optimal, with patients having a 5-year OS of 100% with 90% tumor resection. Low doses of radiation are as effective as high doses and are better tolerated. Additionally, radiation followed by PCV chemotherapy caused major increases in OS. Temozolomide also offers a favorable toxicity profile and QOL; additionally, seizure reduction is an early and consistent prognostic marker for survival after treatment with Temozolomide. CONCLUSIONS: The “wait and see” approach for treatment is no longer the standard for LGGs. Immediate treatment after diagnosis is recommended. Gross total resection (if achievable) is the most favorable treatment, with the highest OS and QOL. The use of chemotherapy and radiotherapy is recommended. Histological background and genetic markers are vital for determining a treatment plan. ACTR-56. UPFRONT CHEMORADIOTHERAPY IN GRADE 2 LOW GRADE GLIOMA, A SINGLE INSTITUTION EXPERIENCE Robert T. Wicks, MD1, Dineth Bandarage2, Ryan T. Mott1, Roy E. Strowd1, Adrian W.  Laxton1, Stephen B.  Tatter1, Michael D.  Chan1 and Glenn J. Lesser1; 1Wake Forest Baptist Medical Center, Winston-Salem, NC, USA, 2Wake Forest University School of Medicine, Winston-Salem, NC, USA BACKGROUND: A recent randomized phase III study demonstrated survival improvement with chemoradiotherapy (CRT) over radiotherapy (RT) alone for WHO Grade II gliomas (LGG). PCV chemotherapy, utilized in this trial, is not commonly used in the US. We analyze our retrospective dataset of predominantly temozolomide-based CRT. METHODS: Retrospective review of 111 LGG patients (years 2000–2013) in a single institution pathology database was performed. We identified 51 patients with LGG that were treated with upfront RT. Characteristics including age, gender, high-risk features (age≥40, tumor size>6 cm, tumor crossing midline, neurologic deficit at diagnosis), and use of RT and chemotherapy were determined. 16 patients received CRT (14 of which received temozolomide), and 35 patients received RT alone (median dose 54Gy). 46 patients had high risk LGG (15/16 receiving CRT, 31/35 receiving RT alone). Survival and progression free survival, based on serial imaging and electronic medical records, were assessed. Kaplan Meier analysis was used to assess time to events, and log rank test was used to compare patients who received RT to those receiving CRT. RESULTS: 5-year progression free survival for patients receiving CRT was 72% versus 54% in patients receiving radiation alone (p=0.03). 5-year overall survival for patients receiving CRT was 93% versus 79% in patients receiving radiation alone (p=0.04). Cox Proportional Hazards analysis revealed that patients with biopsy alone (HR=7.24, p=0.03), RT alone (HR=4.08, p=0.04) and having neurologic deficit at presentation (HR=4.57, p<0.01) had increased risk of death. Cox Proportional Hazards analysis showed that use of upfront RT was the only factor that increased the risk of earlier recurrence (HR=2.72, p=0.03). CONCLUSION: Use of upfront predominantly temozolomide-based CRT had overall survival benefit over RT alone in a population of WHO grade II gliomas treated. CRT was the only factor in this study that predicted for improved time to recurrence. ACTR-57. TEXTILOMA-AN UNUSUAL MIMIC OF BRAIN TUMOR RECURRENCE: A CASE SERIES Deborah  Forst1, Derek  Oakley2, Tracy  Batchelor3 and Jorg  Dietrich4; 1Massachusetts General Hospital, Boston, MA, USA, 2Department of Pathology, Massachusetts General Hospital, Boston, MA, USA, 3Stephen E.  and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, 4Harvard Medical School, Boston, MA, USA OBJECTIVE: To report a single-institution series of five cases of postoperative intracranial textiloma formation mimicking tumor recurrence or progression. BACKGROUND: Textiloma is a rare enhancing mass lesion caused by an inflammatory reaction to retained foreign material following surgery. This may be a response to a larger retained object such as a surgical sponge or gauze, or from a robust reaction to microscopic cotton or rayon fibers, or other synthetic hemostatic agents. Textiloma formation has been reported as an acute post-operative surgical complication, or may occur months to years after surgery. More commonly described after intra-abdominal surgeries, there are only a few anecdotal reports of spinal or intracranial textiloma in the literature. DESIGN/METHODS: Retrospective analysis of imaging and clinical features in 5 patients with textiloma. RESULTS: We identified 5 patients (age from 29 to 54 years; median 30 years) with underlying glioma (n=4) and glioneuronal tumor (n=1). In all five cases, brain MRI demonstrated a peripherally enhancing lesion, commonly with restr

neuro-oncology

ACTR-54. PHASE I TRIAL OF GENETICALLY MODIFIED HEMATOPOETIC PROGENITOR CELLS FACILITATING BONE MARROW CHEMOPROTECTION AND ENABLING TMZ/O6BG DOSE ESCALATION RESULTING IN IMPROVED SURVIVAL