Characterization and clinical impact of temozolomide-induced hepatotoxicity in <i>IDH</i> -wild type glioblastoma: A comprehensive analysis of injury patterns, CTCAE grade transitions, and survival outcomes.

e14075 Background: Temozolomide (TMZ) is the cornerstone of glioblastoma (GBM) treatment but is associated with potential hepatotoxicity. Real-world data regarding the spectrum of liver function test (LFT) abnormalities, specific injury patterns, and their impact on overall survival (OS) remain limited. We aimed to characterize longitudinal changes in LFTs during TMZ therapy, classify injury patterns, and evaluate survival outcomes in a cohort of IDH-wildtype GBM patients. Methods: This retrospective study included 107 patients with IDH-wildtype GBM treated with TMZ. Serum levels of ALT, AST, ALP, GGT, and bilirubin were assessed at baseline and at peak values during follow-up. Hepatotoxicity was graded according to CTCAE v5.0. Liver injury patterns among patients with Grade ≥2 abnormalities were categorized as hepatocellular, cholestatic, or mixed based on R-ratio and enzyme predominance. OS was estimated using the Kaplan–Meier method and compared using the log-rank test, stratified by LFT toxicity grades. Results: At baseline, 38 patients (36%) exhibited Grade 1 LFT abnormalities, with no Grade ≥2 cases. During TMZ therapy, 95% (102/107) developed at least Grade 1 toxicity, and grade escalation from baseline occurred in 63 patients (59%). Grade ≥2 and Grade ≥3 abnormalities were observed in 37 (34.6%) and 22 (20.6%) patients, respectively. While transaminase elevations were predominantly mild, higher-grade toxicities were more frequently characterized by ALP and GGT elevations. Among Grade ≥2 cases (n=37), the mixed injury pattern predominated (75.7%), followed by cholestatic (16.2%) and hepatocellular (8.1%) patterns. In the Grade ≥3 subgroup (n=22), 95.5% exhibited a mixed pattern. Grade ≥3 events occurred during concurrent chemoradiotherapy (54.5%), adjuvant TMZ (27.3%), or post-adjuvant phases (18.2%). Management of Grade ≥3 toxicity involved TMZ discontinuation (18.2%) or interruption (31.8%); LFTs resolved in 31.8% of these cases. Exploratory survival analysis revealed no significant difference in median OS between patients with or without Grade ≥2 toxicity (16.0 vs 16.0 months; p=0.824) or Grade ≥3 toxicity (17.7 vs 16.0 months; p=0.762). Conclusions: LFT abnormalities are highly prevalent during TMZ therapy for IDH-wildtype GBM, with approximately one-fifth of patients experiencing Grade ≥3 toxicity, predominantly exhibiting a mixed injury pattern. Importantly, higher-grade hepatotoxicity was not associated with compromised OS. These findings support vigilant monitoring and individualized management of LFT elevations without necessarily adversely affecting survival.