Central Nervous System

SS 13 - CNS 2 - Gliomas

98 - Risk Factors for Progression of Low Grade Glioma Following Gross Total Resection and Observation in the Molecular Era

Monday, October 22
11:55 AM - 12:05 PM
Location: Room 004

Risk Factors for Progression of Low Grade Glioma Following Gross Total Resection and Observation in the Molecular Era
V. Varra1, C. M. Leyrer2, M. C. Tom2, J. S. Yu2, K. Kotagal3, C. A. Reddy2, S. T. Chao4, J. H. Suh4, G. H. Barnett5, M. A. Vogelbaum5, M. Ahluwalia6, D. Peereboom6, R. Prayson3, G. Stevens7, and E. S. Murphy4; 1Case Western Reserve University School of Medicine, Cleveland, OH, 2Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 3Cleveland Clinic, Cleveland, OH, 4Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 5Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, 6Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 7Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH

Purpose/Objective(s): According to the low risk arm of RTOG 9802, the amount of residual tumor after surgical resection of low grade glioma (LGG) correlates to risk of recurrence. The purpose of this study is to evaluate risk factors in the molecular era for progression in patients with LGG who undergo gross total resection followed by observation.

Materials/Methods: An IRB-approved database of LGG patients was queried for patients with known molecular information who had received gross total resection (GTR) and were initially observed. Patient demographics and tumor factors were evaluated with respect to local recurrence-free survival (LRFS) and overall survival (OS). Univariate and multivariate Cox proportional hazard ratios as well as Kaplan Meier methods were used to evaluate impact on survival outcome.

Results: For the 182 patients diagnosed with LGG between 1985 and 2014, the median age at diagnosis was 29 years (range: 1-73) and 93 (51%) were female. Median follow up was 97 months. Median tumor size was 27 mm. Pathologic diagnosis included 60 (33%) astrocytomas (astro), 82 (45%) oligodendrogliomas (oligo), and 40 (22%) mixed gliomas. One hundred forty-four (80%) patients had GTR confirmed with imaging. One hundred thirty-seven had known 1p status with loss in 36 (26%), 126 had known 19q status with loss in 32 (25%), and 126 had both known 1p and 19q status, with loss of both in 30 (24%). Ninety-eight had known EGFR status with amplified EGFR in 2 (2.0%), 107 had known p53 status with p53 positivity >10% in 37 (35%), and 118 had known IDH status with 58 (49%) mutated. Median time to local recurrence was 10.2 years. LRFS at five and 10 years was 70% (95% CI: 62-78%) and 51% (95% CI: 42-60.), respectively. OS at 5 and 10 years was 97% (95% CI: 95-100%) and 90% (95% CI: 84-96%) respectively. Factors significant for decreased LRFS on univariate analysis were older age at diagnosis (hazard ratio (HR) 1.0; p=.002), oligo histology (HR 2.1; p=.02 vs. astro; HR 2.5; p=.002 vs. mixed), absence of preoperative seizure (HR 2.2; p=.004), presence of preoperative language deficits (HR 2.8; p=.002), IDH mutated status (HR 3.7, p<.0001), and p53 positivity >10% (HR 2.4; p=.005). Only increased tumor size (HR = 1.0, p<0.0001) was significant for decreased LRFS on multivariate analysis, but IDH mutated status (HR = 2.0, p=0.056) approached significance. LRFS in IDH mutated patients at five and 10 years was 57% (95% CI: 43-70%) and 29% (95% CI: 15-43%) respectively, versus 82% (95% CI: 71-94%) and 72% (95% CI: 58-87%) respectively, in IDH wildtype patients.

Conclusion: LGG patients who initially undergo GTR and are observed have prolonged LRFS and excellent OS. In the molecular era, preoperative tumor size remains predictive for LRFS for these low risk LGG.

Author Disclosure: V. Varra: None. C.M. Leyrer: None. J.S. Yu: None. K. Kotagal: None. S.T. Chao: Honoraria; Varian Medical Systems, Zeiss, Abbvie. Consultant; Abbvie. J.H. Suh: Consultant; ACMUI. Board member; Korean American Society for Therapeutic Radiation. G.H. Barnett: None. M.A. Vogelbaum: Consultant; NeuralStem, Inc. Stock Options; Infuseon, Inc. Royalty; Infuseon, Inc. Patent/License Fees/Copyright; Infuseon, Inc. Executive Committee Member; Tumor Section of the AANS/CNS. M. Ahluwalia: Research Grant; Novocure, Novartis. Consultant; Monteris Medical Inc, Incyte. Chair of the Education Committe; American Society of Clinical Oncology. Chair of the Education Day, Annual Meeting; Society of NeuroOncology.

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