IMG-90. Radiographic enhancing progression without molecular or histologic progression in IDH-mutant grade 2 astrocytoma treated with an IDH Inhibitor: A case report

Abstract Grade 2 IDH-mutant astrocytomas are classified as low-grade gliomas with slow growth for many years followed by eventual malignant transformation and death. Here, we present a case of a patient with an IDH-mutant grade 2 astrocytoma who developed early tumor progression per Response Assessment in Neuro-oncology (RANO) 2.0 as evidenced by new enhancement on MRI T1 post-contrast four months after initiation of an IDH inhibitor. Subsequent re-resection of enhancing signal retained Grade 2 designation without any histological or molecular progression per CNS WHO 2021 criteria. Specifically, Ki-67 proliferative index remained stable at approximately 2% and copy number alterations were largely unchanged, including no CDKN2A/B homozygous deletion and relatively low chromosome copy number complexity. On histological examination, there was no elevation in mitotic activity and no features of necrosis, or microvascular proliferation to suggest a more aggressive phenotype. The tumor demonstrated increased gemistocytic morphology and rare foci of foamy macrophages, as compared to prior. Following the second resection, the patient received sequential radiation therapy and adjuvant temozolomide chemotherapy treatment, and has remained clinically stable on observation with surveillance MRIs for over 18 months. This case highlights the importance of re-resection in IDH-mutant gliomas, the potential limitations of the RANO criteria in differentiating treatment effect from true tumor progression, and emphasizes the need for ongoing investigation into novel genetic alterations, molecular signatures, and histologic markers to more accurately predict tumor behavior and guide more personalized, targeted treatment strategies for patients with IDH-mutant gliomas.