2568 - CDKN2A/B Alterations are Associated with Worse Prognosis in IDH Mutated 1p/19q Co-Deleted Oligodendrogliomas

W. X. Mai¹, A. Swamy¹, J. Ho¹, K. Z. Flores¹, B. Eldred², Q. Li², T. F. Cloughesy², A. Lai², and S. G. Soltys¹; ¹Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, ²University of California Los Angeles, Los Angeles, CA

Purpose/Objective(s): In IDH-mutant (mt) lower grade gliomas, homozygous deletion in CDKN2A/B (CDK-del) is an adverse prognostic marker. For astrocytomas, in recognition of a worse prognosis, tumors with CDK-del are upgraded to grade 4 in WHO 2021. Similarly, IDH-mt 1p/19q co-deleted oligodendrogliomas with CDK-del or chromosome 9p aberrations, where the CDKN2A/B locus resides, have a worse prognosis than their wildtype counterpart. However, given the rarity of this subtype, no consensus exists on how to classify and treat this subtype of oligodendrogliomas. In this preliminary analysis of an ongoing multi-institutional retrospective database of oligodendrogliomas, we hypothesize that CDK-del and associated chromosomal aberrations are adverse prognostic markers. Materials/

Methods: This multi-institutional retrospective analysis comprises of over 5 major cancer institutes with ongoing accrual. Clinical information from molecularly confirmed oligodendrogliomas (IDH-mt 1p/19q co-del) are being collected. This includes histologic, pathologic, and molecular details, comprehensive course of treatment(s), patient outcomes, and follow-up data. For this preliminary analysis, median follow up and survival times were calculated using a reverse and regular Kaplan-Meier method, respectively.
Results: Currently, we have identified 20 patients with oligodendroglioma, 17 with CDK-del and 3 with chromosome 9p hemizygous loss. 50%, 39%, and 11% were histologic grade II, III, and IV, respectively. However, WHO grading system varied (2007, 2016, 2021), depending on time of diagnosis. Detailed treatment courses were available for 18 patients. 17 had upfront surgical resection, 65% with subtotal resection. Initial management was observation in 35%, chemotherapy alone in 12%, sequential chemoradiation in 18%, and concurrent chemoradiation in 35%. Of those treated with radiotherapy, 85% received 60 Gy. Chemotherapy regimens were PCV in 25%, TMZ in 67%, and Ivosidenib (IDH inhibitor) in 8%. Outcome data were available for all 20 patients, with a median follow-up of 95 months (IQR 21, 200) and a median survival of 71 months (IQR 46, 214).
Conclusion: Preliminary analyses suggest CDKN2A/B homozygous deletion and associated chromosomal aberrations are adverse prognostic markers for oligodendrogliomas with a median survival approximately 40% of what is expected from historical comparisons of patients with predominantly wild-type CDK (e.g. median survival of 14.7 years in RTOG 9402). CDK-del was previously reported to be mutually exclusive with WHO grade II oligodendroglioma; this was not observed in our data. Further data collection are ongoing, with the goal of improving the classification and possibly, treatment recommendations for this subset of oligodendrogliomas (IRB 69688).