Characterizing malignant transformation in patients with IDH-mutant glioma.

Abstract

2065 Background: Gliomas, which constitute the majority of primary brain cancers in adults, are assigned to a particular grade based on histological and molecular criteria set forth by the World Health Organization (WHO). A subset of initially low grade glioma patients transition to a higher grade at recurrence through a process known as malignant transformation (MT). Despite its significant implications on clinical prognosis, MT remains a poorly understood phenomenon in regards to its incidence rates, effects on survival, and potential prognostic factors. Our study aims to elucidate MT in patients that possess a mutation in the isocitrate dehydrogenase ( IDH) gene, one of the most common genetic alterations in gliomas. Methods: All known IDH mutant glioma patients, seen at UCLA between 1986 and 2022, who received at least 1 repeat resection for presumed recurrent disease were included. Based on surgical pathology reports, patients were categorized into MT and non-transforming progression groups, and further stratified by diagnosis in compliance with the 2016 WHO Classification of Tumors of the Central Nervous System. Relevant clinical information, including patient demographics, survival data, tumor microscopic descriptions, and magnetic resonance imaging, was accessed via electronic medical records. Kaplan Meier analyses were conducted to evaluate the predictive power of various clinical, pathological, and radiological markers. Results: Of 724 total IDH mutant patients screened, 253 received a second surgery and were thus incorporated in this study. Among the 196 patients with lower grade pathologies capable of MT, 129 (65.8%) progressed to a higher grade at recurrence while 71 (36.2%) did not. By diagnosis, the incidence rates of MT for initial grade 2 astrocytomas, grade 3 astrocytomas, and grade 2 oligodendrogliomas were determined to be 74.7%, 48.9%, and 66.1%, respectively. MT was associated with worse overall survival and post-recurrence survival compared to non-transformation in astrocytomas, a trend not seen in oligodendrogliomas. Across all relevant diagnoses, a subset of 36 MT patients did not receive treatment in the interval between initial and recurrent surgery, demonstrating the existence of spontaneously occurring MT. Furthermore, consolidating data from pathology and MRI reports revealed that a greater extent of abnormal molecular characteristics at initial diagnosis and earlier post-operative contrast enhancement may predict MT. Conclusions: These results highlight the distinct nature of gliomas that undergo MT, particularly in tumors of astrocytic differentiation. Considering its adverse impact on clinical outcome, understanding and anticipating this phenomenon is instrumental for the determination of optimal treatment among glioma patients.