A Retrospective, Nationwide, Multicenter Study on Diagnosis and Treatment Outcome of Pediatric Optic Pathway/Hypothalamic Gliomas Including Analysis of Risk Factors for Progression After Systemic Anticancer Therapy

<b>Background:</b> The current standard therapy for pediatric optic pathway/hypothalamic glioma (OPHG) is systemic anticancer therapy (SAT) over surgery and radiotherapy. Nevertheless, recurrent radiological or clinical tumor progression after SAT forms a considerable challenge. Sporadic OPHGs are considered to have a higher tendency toward progression after first-line systemic anticancer therapy (SAT) compared to neurofibromatosis type-1-associated (NF1) OPHGs. <b>Methods:</b> The objective of this study was to conduct a national retrospective cohort analysis of children who received various treatments for a progressive OPHG, involving the hypothalamus and/or chiasm and/or optic radiations. The study aimed to examine the differences in clinical course and the range of treatment modalities applied to both sporadic and NF1-associated OPHGs between 1995 and 2020. Additionally, we sought to identify risk factors for 3- and 5-year progression following first- and second-order SAT. <b>Results:</b> In total, 136 children received treatment, of whom 49 of 136 (36.0%) had NF1. Within a median of 7.5 years (range: 0.1-23.8 years) of follow-up, sporadic OPHGs received more treatments compared to NF1-associated OPHGs (median of 2 (range: 1-8) vs. median of 1 (range: 1-7) (<i>p</i> < 0.01)). Nine children with sporadic OPHGs (6.6%) died. Of 112 children (82.4%) receiving SAT, 92% received combined first-line vincristine and carboplatin. These children had a 3- and 5-year progression-free survival of 61.8% (95% CI: 51.0-72.6%) and 48.4% (95% CI: 38.0-58.8%), respectively. Sporadic OPHGs had a higher rate of second progression (<i>p</i> < 0.01). Starting first-line vincristine and carboplatin at an age below one year was the only independent risk factor for progression. <b>Conclusions:</b> In this national historic cohort of pediatric OPHGs, four out of five children received SAT. Sporadic OPHGs received a higher number of various SATs compared to NF1-associated OPHGs, but the sporadic appearance of OPHGs was not an independent risk factor for progression after combined vincristine and carboplatin, as 'age below one year at the start' was the only factor.