RARE-63. MULTICENTRIC GLIOMA IN OLLIER DISEASE: A CASE REPORT AND REVIEW OF THE LITERATURE

Abstracts intrathecal cytarabine. Here, we describe three patients with IVL. They presented with focal neurological deficits and radiographic evidence of CNS involvement. All 3 IVL patients were treated with rituximab, cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC). This report will describe clinical presentation, response to treatment, complications, and progression and overall survival of these patients. Their presentations highlight the diagnostic and therapeutic challenge in the management of this occult entity. OBJECTIVE: To discuss a case of multicentric glioma in a patient with Ollier disease (OD) and review the literature surrounding this association. BACKGROUND: OD is a subtype of multiple enchondromatosis, characterized by hamartomatous proliferation of chondrocytes in long bones. Extra-osseous tumors have been increasingly reported in this condition, with a particular predisposition towards gliomagenesis. METHODS: Presentation of an illustrative case and literature review of gliomas in patients with OD. RESULTS: A 26-year-old male with OD initially presented at age 15 years with a left skull base chondroma. This dedifferentiated to a chondrosarcoma, requiring resection and radiation therapy. At age 22 years, bifrontal MRI changes consistent with low-grade glioma were identified. Biopsy of the right frontal lesion demonstrated oligodendroglioma, IDHmutant, 1p/19q-codeleted, WHO grade II. Despite adjuvant chemotherapy with temozolomide (TMZ), there was radiographic progression after treatment discontinuation. TMZ therapy was resumed; however, radiographic progression of the left frontal lesion led to surgical resection. A histologic diagnosis of anaplastic oligodendroglioma, WHO grade III, was rendered. Despite radiation therapy and adjuvant procarbazine and lomustine, the left frontal lesion demonstrated enlargement and high-grade features; repeat resection yielded an integrated diagnosis of glioblastoma, IDH-mutant, negative for 1p/19q codeletion (1p loss, 19q intact). CONCLUSIONS: This case reinforces the association between OD and gliomagenesis. Additionally, multicentric glioma in OD is exceptional. The mutant isocitrate dehydrogenase (IDH) 1 pathway in this patient’s gliomas may represent the driving oncogenic pathway for his condition. Increasing evidence supports the concept of somatic heterozygous mutations of IDH1 and IDH2 playing a central role in tumorigenesis in OD, with this aberrant pathway contributing to the development of both mesenchymal and glial tumors. Further characterization of gliomas in OD is essential to our understanding of their pathogenesis, and may illuminate potential therapeutic avenues for glioma arising in the setting of OD. RARE-65. DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: 13 CASES OF A RARE CONDITION Jill Goslinga1, Corey Gill1 and Tracy Batchelor2; 1Massachusetts General Hospital, Boston, MA, USA, 2Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA OBJECTIVE/BACKGROUND: This report will summarize key clinical features of thirteen cases of dysembryoplastic neuroepithelial tumor (DNET), a rare brain tumor that can cause intractable seizures. METHODS: Thirteen cases of DNET were identified from patient records at the Massachusetts General Hospital Brain Tumor Center. Key clinical features were extracted from each patient’s record for this summary report. The study database is approved by the institutional IRB. RESULTS: Among the thirteen cases identified, 9 patients were female and 4 were male; median age at diagnosis was 39.2 years (range 24.3 - 68.4). Initial symptoms at presentation were most commonly seizures (n=11) and rarely sensory changes (n=1); one case discovered incidentally was asymptomatic at diagnosis. Radiographic appearance was most commonly T1 non-enhancing (n=8) and T2 hyperintense (n=9), but three cases were T1 enhancing. Tumor location was most commonly temporal (n=10) and less commonly frontal (n=2) or parietal (n=1). Nearly all patients were treated with gross total resection (GTR, n=12) but one patient received subtotal resection (STR, n=1). After surgical treatment, nearly all patients were progression-free (n=12), but one case of progression resulted in repeat surgery 4 months after initial surgery (n=1). Key post-surgical neurological deficits included seizures (n=2), memory deficits (n=2), and weakness (n=1); 5 patients were neurologically asymptomatic post-surgery, and post-surgical deficits were unknown in 3 of 13 patients. Median patient follow-up duration was 5.2 years (range 0.67 to 17.0 years) and no deaths were reported. CONCLUSIONS: This case series highlights key clinical themes in DNET vi172 NEURO-ONCOLOGY • NO VE M BE R 201 6 RADIOBIOLOGY RBIO-01. RADIATION RESPONSES OF 2D AND 3D GLIOBLASTOMA CELLS: A NOVEL, 3D-SPECIFIC RADIOPROTECTIVE ROLE OF VEGF/Akt SIGNALING THROUGH FUNCTIONAL ACTIVATION OF NHEJ Natividad Gomez-Roman and Anthony Chalmers; University of Glasgow, Glasgow, United Kingdom Glioblastoma (GBM) is resistant to conventional treatments with dismal prognosis. . Tumours exhibit inherent resistance to radiation and chemotherapy which has been attributed to a subpopulation of cancer cells termed ‘GBM stem-like cells’ (GSC) characterised by multipotentiality and potent tumorigenic capacity. Anti-VEGF antibody bevacizumab increases progression-free survival of GBM patients in combination with standard radio-chemotherapy. We have previously shown that bevacizumab enhanced radiosensitivity of 3D GSC cultures in clonogenic and neurosphere formation assays, but had no effect on radiation responses of 2D GSC. VEGF deprivation was associated with significant radiosensitisation of 3D GSC but had no effect on 2D GSC confirming previous findings with bevacizumab. A correlation between radiosensitivity, increased gammaH2AX and phospho-DNA-PK nuclear foci and increased number of cells undergoing mitotic catastrophe or with micronuclei following radiation treatment. In contrast, increased numbers of foci of the homologous recombination (HR) repair protein Rad51 were observed in radioresistant populations. Our results show that in the 3D model, VEGF signalling is required for optimal NHEJ activation with fast kinetics. This effect allows access to HR repair proteins at the remaining unrepaired DSBs at later time points, facilitating their repair and conferring radiation protection. Detailed analysis of the signalling pathways demonstrated a radioprotective role of the downstream signaling molecule Akt. Specific inhibition of Akt using the small molecule inhibitor MK-2206 increased radiation sensitivity to the same extent as VEGF deprivation in 3D cells, and no additivity was observed when these conditions were combined. To our knowledge this is the first report demonstrating a role for VEGF in the re (...truncated)