Abstract
BACKGROUND: Optic pathway gliomas (OPG) are low-grade tumors (LGG) that affect the precortical visual pathway, representing 3-5% of pediatric brain tumors, more often diagnosed before the age of 5 years. Although histologically benign, due to their location and thus their unresectability, they carry considerable morbidity, bringing to progressive visual loss. In up to 20% of cases they are detected in patients with neurofibromatosis type 1 (NF1). Consolidated chemotherapy regimen with or without biopsy or debulking, if feasible, remains so far the standard management, moving to new personalized frontiers. MATERIAL AND METHODS: In Meyer Children’s Hospital IRCCS Neuro-oncology Unit in Florence (Italy), from February 2013 to April 2024, for visual impairment at diagnosis or for disease progression, thirty-seven OPG patients (female/male ratio 1.3, median age at onset 4 years) completed the first line LGG chemotherapy (carboplatin-etoposide scheme adopted in our institution, built upon the INT Milan strategy and the standard SIOP LGG trial). Fourteen patients (37.8%) presented NF1-related OPG diagnosis, mostly made on a clinical/neuroradiological data. Response was assessed according to RAPNO criteria. RESULTS: Non-NF1 OPG patients debuted at a lower median age (3 years) and mostly in a chiasmatic-hypothalamic location, predominantly with a pilocytic astrocytoma histology and manifested with nystagmus, secondarily with visual impairment. Despite the most frequent pre-chiasmatic involvement, during follow-up NF1 patients surprisingly presented a mean and median higher thickness (μm) of the retinal nerve fiber layer (RNFL) on optic coherence tomography (OCT) compared to non-NF1 patients, tested in the majority of patients (mean right RNFL 74.4 versus 58.0, median 66.0 versus 50.0, mean left RNFL 77.2 versus 55.3, median 73.0 versus 49.5). Four non-NF1 patients progressed during treatment or immediately afterwards. Considering the whole follow-up from the stop therapy (median time 5 years), non-NF1 patients progressed by far much more (15/23, 65.2% with one death versus 2/14, 14.3%). Overall survival was 97.3%. CONCLUSION: NF1-related and not related pediatric OPG represent two distinct subgroups, with different clinical and prognostic characteristics. In agreement to other series our data show that non-NF1 OPG are less chemotherapy responsive than NF1-related OPG, surely due to the molecular landscape at the basis of tumor growth, warranting the needing of precision medicine directed to targets also in first- line treatment. A worse OCT outcome was found in the former cohort.