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  • The Majority of Primary Glioblastoma Long-Term Survivors are Not IDH-1 Mutation-Positive

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    J. Manuel Sarmiento BA; Debraj Mukherjee MD, MPH; Keith L. Black MD; Xuemo Fan MD; Jethro Hu; Diana Ly MPH; Miriam Nuno PhD; Chirag G. Patil MD MS

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    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: It is estimated that 3-5% of glioblastoma (GBM) patients are long-term survivors (LTS), as defined by survival of more than 3 years. Given the improved survival conferred by IDH-1 mutations and the fact these mutations are detected in 3-12% of newly diagnosed GBM cases, could long-term survivorship be explained by IDH-1 mutation status? The objective of our study was to assess what proportion of our GBM LTS had IDH-1 mutations.

    Methods: The records of 453 newly-diagnosed adult GBM patients treated at a single institution from 2004 to 2011 were retrospectively reviewed for patients who survived at least 36 months following their initial surgery. Descriptive statistics for clinical characteristics, treatments received, and tumor biomarkers were reported. Kaplan-Meier survival estimates were provided for progression-free and overall survival.

    Results: Forty LTS GBM patients (8.8%) were identified, with a median age of 50 years old and a median Karnofsky Performance Scores (KPS) of 80. Of the 35 patients with available tumor samples, 8 (22.9%) had IDH-1 mutations. IDH1 mutation patients had longer time to progression than non-IDH1 (46.6 vs. 26.3 months, log rank p=.45). Overall survival rates at 48 months were higher with IDH1 mutation (75.0% vs. 56.3%). Most patients underwent near/gross-total resection (72.5%), postoperative radiation (97.5%), and adjuvant temozolomide (95%). Eleven (27.5%) patients received dendritic cell (DC) vaccine therapy. Median progression-free survival (PFS) was 27.6 months .with 40%, 32.7%, and 26.2%; PFS rates at 36, 48, and 72 months, respectively. Median overall survival has not yet been reached; however, survival rates at 48 and 72 months were 62.1% and 49.7%, respectively.

    Conclusions: GBM LTS with IDH-1 mutations trended towards a longer time to progression as well as higher overall survival rates up to 60 months than LTS with wild type IDH-1. However, our patients’ long-term survivorship was not explained by a favorable IDH-1 status.

    Patient Care: Our research provides new prognostic information regarding glioblastoma long-term survivors (patients who survive longer than 3 years). We show that IDH-1 mutation-positive status does not completely explain why some primary glioblastoma patients become long-term survivors. These results show that while IDH-1 mutation-positive status does confer increased survival in glioblastoma patients, it does not necessarily predict long-term survivorship. This information allows neurosurgeons, neuro-oncologists, and palliative care physicians to provide realistic expectations to glioblastoma patients during the shared medical decision process.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe what defines a glioblastoma long-term survivor, 2) Describe what percentage of newly diagnosed glioblastoma patients will become long-term survivors, 3) Describe the characteristics of glioblastoma long-term survivors, and 4) Describe the impact of IDH-1 mutation-positive status in determining glioblastoma long-term survivorship.


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