Biom-53. Prognostic Value of Time to Progression After Initial Treatment of Idh-Mutant Lower-Grade Gliomas (Lgg)

BACKGROUND Miller et al., Neuro Oncol. 2019 proposed that progression free survival (PFS) after first recurrence (PFS2) was a relevant endpoint for IDH-mutant LGG trials. We hypothesized that initial treatment impacted PFS2. METHODS We performed a retrospective analysis of 265 IDH-mutant LGG seen at the University of Virginia between 1/2002 – 8/2024. Progression was verified using the RANO 2.0 criteria for LGG. Median survival times were estimated using the Kaplan-Meier method. Hazard ratios (HR) were from multivariable Cox regression models, and associated p-values were calculated from Wald tests. Age, sex, 2021 WHO CNS tumor classification, and the type and order of treatment received were included as covariates in multivariable models. RESULTS After a median follow-up of 6.4 years, there were 136 (51%) patients who had first progression and 50 deaths (19%). Median PFS after diagnosis (PFS1) was 6.9 years (95% CI: 5.6–8.3) and overall survival (OS) was 19.7 years (95% CI: 16.8–NE: not estimable). Subsequently, 67 (49%) patients had a second progression during a median follow-up of 4.0 years. Median PFS2 was 4.1 years (95% CI: 3.2–5.8) and survival after first progression (OS2) was 11.6 years (95% CI: 7.8–NE). In multivariable analyses, patients who received upfront chemotherapy, then radiation (RT) at progression (HR = 0.38, p = 0.012) or surgery alone, then RT at progression (HR = 0.08, p < 0.001) had improved PFS2 compared to upfront RT and chemotherapy. In a subgroup analysis incorporating extent of resection, patients who received upfront RT and chemotherapy (HR = 18.6, p < 0.001) had shorter PFS2 compared to those who were observed after a biopsy or subtotal resection. CONCLUSION Upfront radiation and chemotherapy had significant influence on PFS2. Thus, treatment history should be considered in the interpretation of PFS2 as a surrogate prognostic marker of OS.