JS01.5.A MEK-INHIBITORS VS CHEMOTHERAPY ACCORDING TO SIOP-LGG2004 PROTOCOL: VISUAL, TOMOGRAPHIC AND CLINICAL FINDINGS IN MONOCENTRIC COHORT OF PEDIATRIC PATIENTS AFFECTED BY OPTIC PATHWAY GLIOMA

Abstract BACKGROUND Chemotherapy still represents the standard first-line treatment for symptomatic or progressive optic pathway gliomas (OPGs)(Falzon et al., 2018). Recently, MEK inhibitors (MEKi) have emerged as a promising therapeutic alternative; however, limited data are available regarding optical coherence tomography (OCT) findings in OPG patients treated with MEKi (Parrozzani et al, 2018). This study aimed to evaluate visual outcomes, with a particular focus on novel data concerning peripapillary retinal nerve fiber layer (pRNFL) (Shlobin et al., 2018) thickness, in children treated with MEKi compared to those treated with the SIOP-LGG 2004 protocol. METHODS This retrospective observational study included children diagnosed and treated for OPGs at Bambino Gesù Children’s Hospital between January 2018 and November 2024. Demographic data, optical coherence tomography (OCT) measurements, magnetic resonance imaging (MRI) findings, and toxicity assessments (graded according to CTCAE v5.0) were collected at predefined time points. RESULTS The study included 15 pediatric patients (mean age of 62.73 months, range 8-208 months) with OPG diagnosis, treated with two different approach. Seven patients (46.67%) received chemotherapy, while eight patients (53.33%) were treated with MEKi after disease progression during chemotherapy. No statistically significant differences were found in pRNFL thickness and visual acuity (VA) between the two groups at baseline (p > 0.05). After 18 months of treatment, VA was better in the MEKi group compared to the SIOP-LGG 2004 protocol group (p = 0.038), while there was no significant difference in pRNFL thickness (p > 0.05), which remained stable in both groups compared to baseline. No significant difference in the best response to treatment was observed between the groups, as assessed by the RAPNO score (p > 0.05). Patients treated with MEKi experienced fewer Grade 1-2 ztoxicity adverse events, with six patients reporting mild skin toxicity and one developing Grade 4 elevated liver enzymes. In contrast, all patients in the chemotherapy group experienced Grade 1-2 gastrointestinal symptoms, three patients experienced Grade 2 hematological toxicity, two patients reported Grade 2 peripheral neuropathy, and three patients experienced Grade 4 allergic reactions to carboplatin. CONCLUSION MEK inhibitors showed superior visual acuity outcomes compared to chemotherapy; OCT findings revealed stable pRNFL thickness in both groups. These results suggest that MEK inhibitors may represent a promising alternative and preferred treatment option for pediatric optic pathway gliomas, considering the reduced toxicity and potentially greater cost-effectiveness.