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Abstract BACKGROUND Infant chiasmatic gliomas present a major therapeutic challenge due to large size, threat to vision and progressive nature. Infants 1 year respond poorly to Vincristine/Carboplatinum chemotherapy (SIOP-LGG2). BRAF fusion is common, so MEK inhibitors have been used second line in older children, but time to response is slow (median ~20 months). Data on the use of these drugs in infants is limited as is data on the safety and efficacy of combining chemotherapy with MEK inhibitors. METHODS We report two infants treated successfully for BRAF fused chiasmatic glioma - both presented age 5 months with nystagmus and diencephalic syndrome. Both had significant tumor progression within 6 weeks of starting Vincristine/ Carboplatin which responded rapidly to the addition of Trametinib. RESULTS Case 1 required tumor debulking at week 6 of chemotherapy due to progressive hyponatremia, hydrocephalus and brainstem compression. Surgery caused diabetes insipidus, hemianopia and hemiparesis. Tumor growth continued despite reinstating chemotherapy. Addition of trametinib caused tumor shrinkage by 75% within 12 weeks and 90% by 1 year. Minirin doses were reduced by 80% on Trametinib. After 1.3 years, chemotherapy was stopped & Trametinib continued alone. Case 2 - tumor growth and severe hyponatremia by week 6 of chemotherapy prompted addition of Trametinib without surgery. There was tumor reduction of 50% over 6 months and improvement of severe failure to thrive. Hyponatremia, requiring sodium and urea supplementation, stabilized. Bilateral vision and age-appropriate development are maintained. Hypertension developed early, but resolved completely after stopping and then gradually reintroducing Trametinib. Recurrent diarrhea required dose reduction. CONCLUSIONS We show the safety and efficacy of combined treatment with chemotherapy and MEK inhibition in infants and postulate that both the combination and the young age at initiation of therapy may have contributed to the excellent outcome. We urge for clinical trials of combination therapy in this age group.
Toledano et al. (Tue,) studied this question.