Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor.

Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal tumors include BRAF mutations and oncogenic fusions. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%), consistent with previously published reports. In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One-patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient's targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1, and ALK (anaplastic lymphoma kinase) inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment magnetic resonance imaging study. The radiologic response was associated with resolution of his clinical symptoms and was maintained for 11 months on treatment. This report of a BCAN-NTRK1 fusion in glioneuronal tumors highlights its clinical importance as a novel, targetable alteration.

Novel pattern of levodopa-related motor fluctuations: 'paradoxical'on.

Generally, motor functions of Parkinson disease (PD) patients become worse as levodopa wears off. Recently, we encountered four PD patients who reported that their motor functions get better after levodopa wears off. These patients were admitted and the pattern of motor fluctuations was monitored. All showed a novel pattern where motor function spontaneously got better near to on level without medication after the effect of levodopa wore off. We call this 'paradoxical'on because motor functions get paradoxically better when levodopa is most likely washed out from the body. Pathomechanism of 'paradoxical'on is uncertain and needs further investigation.