Abstract Background The finding of RAS/MAPK pathway alterations in the majority of pediatric low-grade gliomas (p-LGG) has resulted in a transition from chemotherapy to targeted therapy as initial treatment. While tumor progression after chemotherapy generally led to recommendation of a second-line chemotherapy, it has been suggested that targeted therapy patients could still benefit from resumption of the same targeted treatment in the event of early local tumor progression following elective cessation. Methods We retrospectively reviewed our experience with targeted treatment of p-LGG since the 2021 World Health Organization classification of tumors of the central nervous system, which incorporated molecular features. Following maximal safe resection, patients had disease status assessed serially by Response Assessment in Neuro-Oncology (RANO) criteria. Results We identified three patients with p-LGG who received targeted therapy at initial tumor progression, completed a planned 2-year course in stable disease status, had early local tumor progression on the next MRI, and resumed the identical targeted therapy. Diagnoses were diffuse leptomeningeal glioneuronal tumor (KIAA1549-BRAF fusion) and pleomorphic xanthoastrocytoma and ganglioglioma (BRAF V600E mutation), treated with trametinib and dabrafenib/trametinib respectively. All patients had PR at 10 weeks to 3 months from resumption of targeted therapy, but with PD at 8 and 13 months in 2 patients, while one remains SD at 20+ months. Conclusions Resumption of identical targeted therapies for p-LGG following elective cessation was transiently effective, but other strategies could provide more prolonged disease control.
Lardieri et al. (2025) studied this question.