2543 - Association of Age with IDH-Status and Progression in Diffuse Gliomas

C. J. Kinslow¹, A. Mercurio², P. Kumar², M. Siegelin², E. Kocakavuk³, G. M. McKhann⁴, M. B. Sisti⁴, J. N. Bruce⁴, P. Canoll⁵, F. Iwamoto², D. P. Horowitz⁶, A. I. Neugut², L. A. Kachnic², P. D. Brown⁷, S. K. Cheng⁸, and T. J. C. Wang²; ¹Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY, ²Columbia University, New York, NY, ³University of Duisburg-Essen, Essen, Germany, ⁴Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY, ⁵Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, ⁶Columbia University Irving Medical Center, New York, NY, ⁷Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ⁸Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY

Purpose/Objective(s): Age greater than 40 years is considered a high-risk feature and potentially an indication for chemoradiotherapy for low-grade gliomas based on studies conducted in the pre-molecular era. Older age is associated with IDH-wildtype status and may not have independent prognostic value. Materials/

Methods: The Prospective Glioma Research (PROGRES) Database is a multi-institutional collaborative effort intended to interrogate the effects of molecular classification on glioma outcomes. We aggregated grade II and III primary glioma data from 4 prospectively enrolled cohorts (MSK-IMPACT, EORTC 26951, Columbia University, CODEL) for pooled analysis.¹ The Kaplan-Meier method and Cox proportional hazards regressions were used to access the association of age >40 years with progression-free survival (PFS). Findings were validated in publicly available datasets.
Results: We identified 627 patients with histological grade 2-3 gliomas. For patients <40 years, only 11% of gliomas were IDH-wildtype compared to 42% in patients >40 years (P < .001). For all patients, age >40 years was associated with poorer PFS (3.0 vs. 6.4 years, P < .001, HR = 1.74 [95%CI 1.39-2.18]). Among patients with IDH-mutant tumors (n=419), age >40 years had no effect on PFS (8.2 vs. 7.5 years, P = .60, HR = 1.08 [95%CI 0.81-1.43]. Age also had no effect on PFS for patients with grade 2 IDH-mutant gliomas (9.1 vs. 9.2 years, P = .90, HR = 1.04 [95%CI 0.65-1.65]). Similar results for PFS were observed for patients IDH-mutant tumors in the TCGA (n=415) and GLASS (n=66) cohorts and for overall survival in the DFCI (n=122) cohort.
Conclusion: Our analysis suggests that age is a surrogate for IDH-status but not an independent risk factor for progression in diffuse gliomas. If these findings are validated within the RTOG 9802, RTOG 0424, and EORTC 22033 trials, there may be sufficient evidence to remove age as an indication for chemoradiotherapy from clinical practice guidelines in the molecular era.